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Wechsler, Daniel Steven Gary

Overview:

Our laboratory is primarily focused on understanding the pathogenesis of childhood leukemias. This interest developed after treating an infant with acute myeloid leukemia (AML), whose leukemia cells carried a novel chromosomal translocation, MLL-CALM. The CALM gene, which encodes for a protein involved in endocytosis, is also found in CALM-AF10 translocations, which are seen in 5-10% of T cell leukemias. In studies to identify which particular domains of CALM contribute to leukemogenesis, we determined that CALM contains a nuclear export signal (NES) that is necessary and sufficient for imparting leukemogenic properties to CALM-AF10. The NES interacts with CRM1/XPO1, a nuclear chaperone protein that is involved in exporting proteins from the nucleus to the cytoplasm. We have recently found that CRM1 contributes to the upregulation of HOXA genes, which are essential mediators of leukemogenesis. We are currently exploring the mechanisms by which CRM1 modulates HOXA gene expression, focusing on mutational analysis of critical CRM1 domains and the identification of CRM1-interacting partner proteins. Given the ability of CRM1 to regulate transcription of HOXA genes, we are also seeking to identify additional non-HOXA CRM1 target genes. Finally, we also take advantage of compounds that inhibit CRM1 function (SINEs - Selective Inhibitors of Nuclear Export) that are being used in both preclinical and early phase clinical trials, to dissect out CRM1-dependent functions.

     The lab uses molecular, cellular and in vivo mouse studies taking advantage of well-established murine leukemia models. By developing a better understanding of CALM and CRM1 function in normal and malignant hematopoiesis, we will be able to develop new therapeutic approaches for difficult-to-treat infant and pediatric leukemias.

Positions:

Associate Professor of Pediatrics

Pediatrics, Hematology-Oncology
School of Medicine

Associate Professor of Pharmacology & Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1987

Ph.D. — McGill University (Canada)

M.D.C.M. 1987

M.D.C.M. — McGill University (Canada)

Pediatric Internship And Residency, Pediatrics

Johns Hopkins University

Pediatric Hematology/Oncology Fellowship, Pediatrics

Johns Hopkins University

News:

Deadly Emoticons

August 08, 2013

Grants:

Pratt Cares Program

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
Pratt Family Foundation, Inc.
Role
Principal Investigator
Start Date
December 01, 2015
End Date
November 30, 2018

SELHEM: Phase I/II (KPT-330)

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
St. Jude Children's Research Hospital
Role
Principal Investigator
Start Date
July 01, 2015
End Date
July 31, 2018

Duke-UNC Clinical Hematology and Transfusion Research Career Development Program

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 28, 2006
End Date
April 30, 2018

An integrated and diverse genomic medicine program for undiagnosed diseases

Administered By
Pediatrics, Medical Genetics
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
July 01, 2014
End Date
March 31, 2018

Expansion of the AYA Oncology Initiative at Duke University

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
St. Baldrick's Foundation
Role
Investigator
Start Date
December 01, 2016
End Date
November 30, 2017

Hematology-Oncology Fellowship Program

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
A.E. Finley Foundation, Inc.
Role
Principal Investigator
Start Date
September 01, 2013
End Date
August 31, 2017

Examine KPT330 in Murine Leukemia Models

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
Karyopharm Therapeutics
Role
Principal Investigator
Start Date
December 18, 2014
End Date
December 17, 2016

Defining A Role for the CRM1 Nuclear Export Protein in Pediatric Leukemias

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
V Foundation for Cancer Research
Role
Principal Investigator
Start Date
February 01, 2015
End Date
September 01, 2016

A Novel Role for the CRM1 in Pediatric Leukemias: Mechanisms and Targeting

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
St. Baldrick's Foundation
Role
Principal Investigator
Start Date
July 01, 2014
End Date
June 30, 2015

A NOVEL ROLE FOR THE CRM1 NUCLEAR EXPORT RECEPTOR IN LEUKEMOGENESIS: MECHANISMS AND TARGETING

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
V Foundation for Cancer Research
Role
Principal Investigator
Start Date
October 01, 2013
End Date
September 30, 2014

St. Baldrick's Summer Fellow Grant

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
St. Baldrick's Foundation
Role
Principal Investigator
Start Date
May 15, 2014
End Date
August 31, 2014

Research Training in Cancer Biology and Therapy

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
August 01, 1978
End Date
July 31, 2013

Mechanisms of Leukemogenic Transformations by MLL-CALM

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
June 01, 2005
End Date
June 30, 2011
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Publications:

A positive feedback loop between ROS and Mxi1-0 promotes hypoxia-induced VEGF expression in human hepatocellular carcinoma cells.

VEGF expression induced by hypoxia plays a critical role in promoting tumor angiogenesis. However, the molecular mechanism that modulates VEGF expression under hypoxia is still poorly understood. In this study, we found that VEGF induction in hypoxic HepG2 cells is ROS-dependent. ROS mediates hypoxia-induced VEGF by upregulation of Mxi1-0. Furthermore, PI3K/AKT/HIF-1α signaling pathway is involved in ROS-mediated Mxi1-0 and VEGF expression in hypoxic HepG2 cells. Finally, Mxi1-0 could in turn regulate ROS generation in hypoxic HepG2 cells, creating a positive feedback loop. Taken together, this study demonstrate a positive regulatory feedback loop in which ROS mediates hypoxia-induced Mxi1-0 via activation of PI3K/AKT/HIF-1α pathway, events that in turn elevate ROS generation and promote hypoxia-induced VEGF expression. These findings could provide a rationale for designing new therapies based on inhibition of hepatocellular carcinoma (HCC) angiogenesis.

Authors
Hu, Z; Dong, N; Lu, D; Jiang, X; Xu, J; Wu, Z; Zheng, D; Wechsler, DS
MLA Citation
Hu, Z, Dong, N, Lu, D, Jiang, X, Xu, J, Wu, Z, Zheng, D, and Wechsler, DS. "A positive feedback loop between ROS and Mxi1-0 promotes hypoxia-induced VEGF expression in human hepatocellular carcinoma cells." Cellular signalling 31 (February 2017): 79-86.
PMID
28065785
Source
epmc
Published In
Cellular Signalling
Volume
31
Publish Date
2017
Start Page
79
End Page
86
DOI
10.1016/j.cellsig.2017.01.007

The 2016 ASPHO Distinguished Career Award Goes to David G. Poplack, MD.

Authors
Blaney, SM; Adamson, PC; Wechsler, DS
MLA Citation
Blaney, SM, Adamson, PC, and Wechsler, DS. "The 2016 ASPHO Distinguished Career Award Goes to David G. Poplack, MD." Pediatric blood & cancer 63 Suppl 1 (June 2016): S5-S6.
PMID
27077669
Source
epmc
Published In
Pediatric Blood & Cancer
Volume
63 Suppl 1
Publish Date
2016
Start Page
S5
End Page
S6
DOI
10.1002/pbc.25978

The role of Exon 0 in mediating Mxi0 activity in neuroblastoma

Authors
Kirchner, SJ; Bartram, JT; Ellis, DC; Wechsler, DS; Armstrong, MB
MLA Citation
Kirchner, SJ, Bartram, JT, Ellis, DC, Wechsler, DS, and Armstrong, MB. "The role of Exon 0 in mediating Mxi0 activity in neuroblastoma." March 1, 2016.
Source
wos-lite
Published In
Cancer Research
Volume
76
Publish Date
2016

THE CRM1 NUCLEAR EXPORT RECEPTOR IS CRITICAL FOR THE EXPRESSION OF HOXA GENES AND CAN SUBSTITUTE FOR CALM IN CALM-AF10 LEUKEMOGENESIS

Authors
Wechsler, D; Heath, J; Aumann, W; Lavau, C
MLA Citation
Wechsler, D, Heath, J, Aumann, W, and Lavau, C. "THE CRM1 NUCLEAR EXPORT RECEPTOR IS CRITICAL FOR THE EXPRESSION OF HOXA GENES AND CAN SUBSTITUTE FOR CALM IN CALM-AF10 LEUKEMOGENESIS." PEDIATRIC BLOOD & CANCER 62 (November 2015): S156-S156.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
62
Publish Date
2015
Start Page
S156
End Page
S156

PEDIATRIC ONCOLOGY IN THE LAKE REGION OF TANZANIA: EVALUATION OF CLINICAL DIAGNOSIS, TREATMENT AND OUTCOMES

Authors
Schroeder, K; Chao, C; Masalu, N; Mafwimbo, S; Mafwimbo, J; Wechsler, D; Chao, N; Likonda, B
MLA Citation
Schroeder, K, Chao, C, Masalu, N, Mafwimbo, S, Mafwimbo, J, Wechsler, D, Chao, N, and Likonda, B. "PEDIATRIC ONCOLOGY IN THE LAKE REGION OF TANZANIA: EVALUATION OF CLINICAL DIAGNOSIS, TREATMENT AND OUTCOMES." PEDIATRIC BLOOD & CANCER 62 (November 2015): S296-S296.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
62
Publish Date
2015
Start Page
S296
End Page
S296

MXI1 AND MXI0 HAVE DIFFERENTIAL IMPACT ON N-MYC FUNCTION IN NEUROBLASTOMA GROWTH AND CHEMOSENSITIVITY

Authors
Ellis, DC; Kirchner, S; Bartram, J; Wechsler, D; Armstrong, M
MLA Citation
Ellis, DC, Kirchner, S, Bartram, J, Wechsler, D, and Armstrong, M. "MXI1 AND MXI0 HAVE DIFFERENTIAL IMPACT ON N-MYC FUNCTION IN NEUROBLASTOMA GROWTH AND CHEMOSENSITIVITY." PEDIATRIC BLOOD & CANCER 62 (November 2015): S224-S224.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
62
Publish Date
2015
Start Page
S224
End Page
S224

Persistent and Prolonged Parvovirus B19 Viremia in a Pediatric Patient With Acute Lymphoblastic Leukemia.

Parvovirus B19 is a small single-stranded DNA virus of the Parvoviridae family. Depending on host factors, it may produce a wide array of clinical disease states. Disease severity can range from self-limited to severe, requiring significant supportive care. Immunocompromised patients are generally affected more severely but rarely develop prolonged and persistent infections. Here, we describe a patient who was diagnosed with parvovirus during maintenance therapy for acute lymphoblastic leukemia and required therapy with intravenous immunoglobulin; the patient remained parvovirus positive according to a polymerase chain reaction testing but had no clinical symptoms for 27 months off chemotherapy.

Authors
Fritch Lilla, SA; Burgett, SE; McGann, KA; Wechsler, DS
MLA Citation
Fritch Lilla, SA, Burgett, SE, McGann, KA, and Wechsler, DS. "Persistent and Prolonged Parvovirus B19 Viremia in a Pediatric Patient With Acute Lymphoblastic Leukemia." Journal of the Pediatric Infectious Diseases Society 4.3 (September 2015): e38-e40.
PMID
26407441
Source
epmc
Published In
Journal of the Pediatric Infectious Diseases Society
Volume
4
Issue
3
Publish Date
2015
Start Page
e38
End Page
e40
DOI
10.1093/jpids/piu112

DIFFERENTIAL EFFECTS OF MXI1 AND MXI0 ON N-MYC-DEPENDENT NEUROBLASTOMA PATHOGENESIS AND CHEMOSENSITIVITY

Authors
Ellis, DC; Kirchner, S; Bartram, J; Wechsler, D; Armstrong, M
MLA Citation
Ellis, DC, Kirchner, S, Bartram, J, Wechsler, D, and Armstrong, M. "DIFFERENTIAL EFFECTS OF MXI1 AND MXI0 ON N-MYC-DEPENDENT NEUROBLASTOMA PATHOGENESIS AND CHEMOSENSITIVITY." PEDIATRIC BLOOD & CANCER 62 (June 2015): 98-98.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
62
Publish Date
2015
Start Page
98
End Page
98

THE CRM1 NUCLEAR EXPORT RECEPTOR ACTIVATES HOXA GENE EXPRESSION IN SEVERAL LEUKEMIA MODELS

Authors
Heath, J; Aumann, W; Conway, A; Lavau, C; Wechsler, D
MLA Citation
Heath, J, Aumann, W, Conway, A, Lavau, C, and Wechsler, D. "THE CRM1 NUCLEAR EXPORT RECEPTOR ACTIVATES HOXA GENE EXPRESSION IN SEVERAL LEUKEMIA MODELS." PEDIATRIC BLOOD & CANCER 62 (June 2015): 24-24.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
62
Publish Date
2015
Start Page
24
End Page
24

A critical role for CRM1 in regulating HOXA gene transcription in CALM-AF10 leukemias

© 2015 Macmillan Publishers Limited All rights reservedThe leukemogenic CALM-AF10 fusion protein is found in patients with immature acute myeloid and T-lymphoid malignancies. CALM-AF10 leukemias display abnormal H3K79 methylation and increased HOXA cluster gene transcription. Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear. We previously determined that CALM contains a CRM1-dependent nuclear export signal (NES), which is both necessary and sufficient for CALM-AF10-mediated leukemogenesis. Here, we find that interaction of CALM-AF10 with the nuclear export receptor CRM1 is necessary for activating HOXA gene expression. We show that CRM1 localizes to HOXA loci where it recruits CALM-AF10, leading to transcriptional and epigenetic activation of HOXA genes. Genetic and pharmacological inhibition of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin, resulting in immediate loss of transcription. These results provide a comprehensive mechanism by which the CALM-AF10 translocation activates the critical HOXA cluster genes. Furthermore, this report identifies a novel function of CRM1: the ability to bind chromatin and recruit the NES-containing CALM-AF10 transcription factor.

Authors
Conway, AE; Haldeman, JM; Wechsler, DS; Lavau, CP
MLA Citation
Conway, AE, Haldeman, JM, Wechsler, DS, and Lavau, CP. "A critical role for CRM1 in regulating HOXA gene transcription in CALM-AF10 leukemias." Leukemia 29.2 (February 7, 2015): 423-432.
Source
scopus
Published In
Leukemia
Volume
29
Issue
2
Publish Date
2015
Start Page
423
End Page
432
DOI
10.1038/leu.2014.221

A critical role for CRM1 in regulating HOXA gene transcription in CALM-AF10 leukemias.

The leukemogenic CALM-AF10 fusion protein is found in patients with immature acute myeloid and T-lymphoid malignancies. CALM-AF10 leukemias display abnormal H3K79 methylation and increased HOXA cluster gene transcription. Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear. We previously determined that CALM contains a CRM1-dependent nuclear export signal (NES), which is both necessary and sufficient for CALM-AF10-mediated leukemogenesis. Here, we find that interaction of CALM-AF10 with the nuclear export receptor CRM1 is necessary for activating HOXA gene expression. We show that CRM1 localizes to HOXA loci where it recruits CALM-AF10, leading to transcriptional and epigenetic activation of HOXA genes. Genetic and pharmacological inhibition of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin, resulting in immediate loss of transcription. These results provide a comprehensive mechanism by which the CALM-AF10 translocation activates the critical HOXA cluster genes. Furthermore, this report identifies a novel function of CRM1: the ability to bind chromatin and recruit the NES-containing CALM-AF10 transcription factor.

Authors
Conway, AE; Haldeman, JM; Wechsler, DS; Lavau, CP
MLA Citation
Conway, AE, Haldeman, JM, Wechsler, DS, and Lavau, CP. "A critical role for CRM1 in regulating HOXA gene transcription in CALM-AF10 leukemias." Leukemia 29.2 (February 2015): 423-432.
PMID
25027513
Source
epmc
Published In
Leukemia
Volume
29
Issue
2
Publish Date
2015
Start Page
423
End Page
432
DOI
10.1038/leu.2014.221

Mxi1 and mxi1-0 antagonize N-myc function and independently mediate apoptosis in neuroblastoma.

Neuroblastoma (NB) is the third most common malignancy of childhood, and outcomes for children with advanced disease remain poor; amplification of the MYCN gene portends a particularly poor prognosis. Mxi1 antagonizes N-Myc by competing for binding to Max and E-boxes. Unlike N-Myc, Mxi1 mediates transcriptional repression and suppresses cell proliferation. Mxi1 and Mxi1-0 (an alternatively transcribed Mxi1 isoform) share identical Max and DNA binding domains but differ in amino-terminal sequences. Because of the conservation of these critical binding domains, we hypothesized that Mxi1-0 antagonizes N-Myc activity similar to Mxi1. SHEP NB cells and SHEP cells stably transfected with MYCN (SHEP/MYCN) were transiently transfected with vectors containing full-length Mxi1, full-length Mxi1-0, or the common Mxi domain encoded by exons 2 to 6 (ex2-6). After incubation in low serum, parental SHEP/MYCN cell numbers were reduced compared with SHEP cells. Activated caspase-3 staining and DNA fragmentation ELISA confirmed that SHEP/MYCN cells undergo apoptosis in low serum, while SHEP/MYCN cells transfected with Mxi1 or Mxi1-0 do not. However, SHEP/MYCN cells transfected with Mxi1 or Mxi1-0 and grown in normal serum showed proliferation rates similar to SHEP cells. Mxi ex2-6 did not affect cell number in low or normal serum, suggesting that amino terminal domains of Mxi1 and Mxi1-0 are critical for antagonism. In the absence of N-Myc, Mxi1 and Mxi1-0 induce apoptosis independently through the caspase-8-dependent extrinsic pathway, while N-Myc activates the caspase-9-dependent intrinsic pathway. Together, these data indicate that Mxi1 and Mxi1-0 antagonize N-Myc but also independently impact NB cell survival.

Authors
Erichsen, DA; Armstrong, MB; Wechsler, DS
MLA Citation
Erichsen, DA, Armstrong, MB, and Wechsler, DS. "Mxi1 and mxi1-0 antagonize N-myc function and independently mediate apoptosis in neuroblastoma." Translational oncology 8.1 (February 2015): 65-74.
PMID
25749179
Source
epmc
Published In
Translational oncology
Volume
8
Issue
1
Publish Date
2015
Start Page
65
End Page
74
DOI
10.1016/j.tranon.2015.01.002

Corrigendum: PICALM modulates autophagy activity and tau accumulation

Authors
Moreau, K; Fleming, A; Imarisio, S; Lopez Ramirez, A; Mercer, JL; Jimenez-Sanchez, M; Bento, CF; Puri, C; Zavodszky, E; Siddiqi, F; Lavau, CP; Betton, M; O'Kane, CJ; Wechsler, DS; Rubinsztein, DC
MLA Citation
Moreau, K, Fleming, A, Imarisio, S, Lopez Ramirez, A, Mercer, JL, Jimenez-Sanchez, M, Bento, CF, Puri, C, Zavodszky, E, Siddiqi, F, Lavau, CP, Betton, M, O'Kane, CJ, Wechsler, DS, and Rubinsztein, DC. "Corrigendum: PICALM modulates autophagy activity and tau accumulation." Nature Communications (January 28, 2015): 6110-6110.
Source
crossref
Published In
Nature Communications
Publish Date
2015
Start Page
6110
End Page
6110
DOI
10.1038/ncomms7110

Modulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis.

PICALM (Phosphatidyl Inositol Clathrin Assembly Lymphoid Myeloid protein) is a ubiquitously expressed protein that plays a role in clathrin-mediated endocytosis. PICALM also affects the internalization and trafficking of SNAREs and modulates macroautophagy. Chromosomal translocations that result in the fusion of PICALM to heterologous proteins cause leukemias, and genome-wide association studies have linked PICALM Single Nucleotide Polymorphisms (SNPs) to Alzheimer's disease. To obtain insight into the biological role of PICALM, we performed gene expression studies of PICALM-deficient and PICALM-expressing cells. Pathway analysis demonstrated that PICALM expression influences the expression of genes that encode proteins involved in cholesterol biosynthesis and lipoprotein uptake. Gas Chromatography-Mass Spectrometry (GC-MS) studies indicated that loss of PICALM increases cellular cholesterol pool size. Isotopic labeling studies revealed that loss of PICALM alters increased net scavenging of cholesterol. Flow cytometry analyses confirmed that internalization of the LDL receptor is enhanced in PICALM-deficient cells as a result of higher levels of LDLR expression. These findings suggest that PICALM is required for cellular cholesterol homeostasis and point to a novel mechanism by which PICALM alterations may contribute to disease.

Authors
Mercer, JL; Argus, JP; Crabtree, DM; Keenan, MM; Wilks, MQ; Chi, J-TA; Bensinger, SJ; Lavau, CP; Wechsler, DS
MLA Citation
Mercer, JL, Argus, JP, Crabtree, DM, Keenan, MM, Wilks, MQ, Chi, J-TA, Bensinger, SJ, Lavau, CP, and Wechsler, DS. "Modulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis." PloS one 10.6 (January 2015): e0129776-.
PMID
26075887
Source
epmc
Published In
PloS one
Volume
10
Issue
6
Publish Date
2015
Start Page
e0129776
DOI
10.1371/journal.pone.0129776

The CRM1 Nuclear Export Receptor Activates HOXA Gene Expression in Leukemogenesis

Authors
Lavau, CP; Heath, JL; Lee, WH; Conway, AE; Wechsler, DS
MLA Citation
Lavau, CP, Heath, JL, Lee, WH, Conway, AE, and Wechsler, DS. "The CRM1 Nuclear Export Receptor Activates HOXA Gene Expression in Leukemogenesis." December 6, 2014.
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

Effects of iron depletion on CALM-AF10 leukemias.

Iron, an essential nutrient for cellular growth and proliferation, enters cells via clathrin-mediated endocytosis. The clathrin assembly lymphoid myeloid (CALM) protein plays an essential role in the cellular import of iron by clathrin-mediated endocytosis. CALM-AF10 leukemias harbor a single copy of the normal CALM gene and therefore may be more sensitive to the growth-inhibitory effect of iron restriction compared with normal hematopoietic cells. We found that CALM heterozygous (CALM(HET)) murine fibroblasts exhibit signs of iron deficiency, with increased surface transferrin receptor levels and reduced growth rates. CALM(HET) hematopoietic cells are more sensitive in vitro to iron chelators than their wild type counterparts. Iron chelation also displayed toxicity toward cultured CALM(HET)CALM-AF10 leukemia cells, and this effect was additive to that of chemotherapy. In mice transplanted with CALM(HET)CALM-AF10 leukemia, we found that dietary iron restriction reduced tumor burden in the spleen. However, dietary iron restriction, used alone or in conjunction with chemotherapy, did not increase survival of mice with CALM(HET)CALM-AF10 leukemia. In summary, although CALM heterozygosity results in iron deficiency and increased sensitivity to iron chelation in vitro, our data in mice do not suggest that iron depletion strategies would be beneficial for the therapy of CALM-AF10 leukemia patients.

Authors
Heath, JL; Weiss, JM; Lavau, CP; Wechsler, DS
MLA Citation
Heath, JL, Weiss, JM, Lavau, CP, and Wechsler, DS. "Effects of iron depletion on CALM-AF10 leukemias." Experimental hematology 42.12 (December 2014): 1022-30.e1.
PMID
25193880
Source
epmc
Published In
Experimental Hematology
Volume
42
Issue
12
Publish Date
2014
Start Page
1022
End Page
30.e1
DOI
10.1016/j.exphem.2014.08.004

Successful treatment of pediatric histiocytic sarcoma using abbreviated high-risk leukemia chemotherapy.

Histiocytic sarcoma (HS) is a malignant tumor composed of proliferating cells of histiocytic origin. True HS is exceedingly rare, particularly in pediatric patients. These tumors are frequently aggressive, and outcome for patients with HS has traditionally been poor. There is currently no consensus on the optimal management of these tumors, with the literature consisting largely of case reports and small case series utilizing a wide variety of therapies. We describe a case of HS in an 8-year-old female who was successfully treated with an abbreviated leukemia chemotherapy regimen.

Authors
Heath, JL; Burgett, SE; Gaca, AM; Jaffe, R; Wechsler, DS
MLA Citation
Heath, JL, Burgett, SE, Gaca, AM, Jaffe, R, and Wechsler, DS. "Successful treatment of pediatric histiocytic sarcoma using abbreviated high-risk leukemia chemotherapy." Pediatric blood & cancer 61.10 (October 2014): 1874-1876.
PMID
24888336
Source
epmc
Published In
Pediatric Blood & Cancer
Volume
61
Issue
10
Publish Date
2014
Start Page
1874
End Page
1876
DOI
10.1002/pbc.25100

The impact of modulating Mxil and Mxi0 expression on N-Myc-mediated neuroblastoma tumor pathogenesis and chemosensitivity

Authors
Ellis, DC; Widemon, RS; Wechsler, DS; Armstrong, MB
MLA Citation
Ellis, DC, Widemon, RS, Wechsler, DS, and Armstrong, MB. "The impact of modulating Mxil and Mxi0 expression on N-Myc-mediated neuroblastoma tumor pathogenesis and chemosensitivity." CANCER RESEARCH 74.20 (October 2014).
Source
wos-lite
Published In
Cancer Research
Volume
74
Issue
20
Publish Date
2014

PICALM modulates autophagy activity and tau accumulation.

Genome-wide association studies have identified several loci associated with Alzheimer's disease (AD), including proteins involved in endocytic trafficking such as PICALM/CALM (phosphatidylinositol binding clathrin assembly protein). It is unclear how these loci may contribute to AD pathology. Here we show that CALM modulates autophagy and alters clearance of tau, a protein which is a known autophagy substrate and which is causatively linked to AD, both in vitro and in vivo. Furthermore, altered CALM expression exacerbates tau-mediated toxicity in zebrafish transgenic models. CALM influences autophagy by regulating the endocytosis of SNAREs, such as VAMP2, VAMP3 and VAMP8, which have diverse effects on different stages of the autophagy pathway, from autophagosome formation to autophagosome degradation. This study suggests that the AD genetic risk factor CALM modulates autophagy, and this may affect disease in a number of ways including modulation of tau turnover.

Authors
Moreau, K; Fleming, A; Imarisio, S; Lopez Ramirez, A; Mercer, JL; Jimenez-Sanchez, M; Bento, CF; Puri, C; Zavodszky, E; Siddiqi, F; Lavau, CP; Betton, M; O'Kane, CJ; Wechsler, DS; Rubinsztein, DC
MLA Citation
Moreau, K, Fleming, A, Imarisio, S, Lopez Ramirez, A, Mercer, JL, Jimenez-Sanchez, M, Bento, CF, Puri, C, Zavodszky, E, Siddiqi, F, Lavau, CP, Betton, M, O'Kane, CJ, Wechsler, DS, and Rubinsztein, DC. "PICALM modulates autophagy activity and tau accumulation." Nature communications 5 (September 22, 2014): 4998-.
PMID
25241929
Source
epmc
Published In
Nature Communications
Volume
5
Publish Date
2014
Start Page
4998
DOI
10.1038/ncomms5998

CRITICAL CONTRIBUTIONS OF CRM1 TO CALM-AF10 LEUKEMOGENESIS

Authors
Heath, J; Conway, A; Lavau, C; Wechsler, D
MLA Citation
Heath, J, Conway, A, Lavau, C, and Wechsler, D. "CRITICAL CONTRIBUTIONS OF CRM1 TO CALM-AF10 LEUKEMOGENESIS." PEDIATRIC BLOOD & CANCER 61 (May 2014): S48-S49.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
61
Publish Date
2014
Start Page
S48
End Page
S49

TARGETING OF CALM-AF10 LEUKEMIAS BY IRON DEPRIVATION

Authors
Heath, J; Lavau, C; Weiss, J; Wechsler, D
MLA Citation
Heath, J, Lavau, C, Weiss, J, and Wechsler, D. "TARGETING OF CALM-AF10 LEUKEMIAS BY IRON DEPRIVATION." PEDIATRIC BLOOD & CANCER 61 (May 2014): S49-S49.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
61
Publish Date
2014
Start Page
S49
End Page
S49

TARGETING CALM-AF10 LEUKEMIA CELLS WITH NUCLEAR EXPORT INHIBITORS

Authors
Lilla, SF; Conway, A; Lavau, C; Wechsler, D
MLA Citation
Lilla, SF, Conway, A, Lavau, C, and Wechsler, D. "TARGETING CALM-AF10 LEUKEMIA CELLS WITH NUCLEAR EXPORT INHIBITORS." PEDIATRIC BLOOD & CANCER 61 (May 2014): S24-S24.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
61
Publish Date
2014
Start Page
S24
End Page
S24

Adolescent and young adult oncology, version 2.2014.

The NCCN Guidelines Insights on Adolescent and Young Adult (AYA) Oncology discuss the fertility and endocrine issues that are relevant to the management of AYA patients with cancer. Fertility preservation should be an essential part in the treatment of AYA patients with cancer. The NCCN Guidelines recommend discussion of fertility preservation and contraception before the start of treatment. Oophoropexy and embryo cryopreservation are the 2 established options for fertility preservation in women. Semen cryopreservation before the start of treatment is the most reliable and well-established method of preserving fertility in men. AYA women with cancer also have unique contraception needs, depending on the type of cancer, its treatment, and treatment-related complications. Management of cancer during pregnancy poses significant diagnostic and therapeutic challenges for both the patient and the physician. AYA women diagnosed with cancer during pregnancy require individualized treatment from a multidisciplinary team involving medical, surgical, radiation, and gynecologic oncologists; obstetricians; and perinatologists.

Authors
Coccia, PF; Pappo, AS; Altman, J; Bhatia, S; Borinstein, SC; Flynn, J; Frazier, AL; George, S; Goldsby, R; Hayashi, R; Huang, MS; Johnson, RH; Beaupin, LK; Link, MP; Oeffinger, KC; Orr, KM; Reed, D; Spraker, HL; Thomas, DA; von Mehren, M; Wechsler, DS; Whelan, KF; Zebrack, B; Shead, DA; Sundar, H
MLA Citation
Coccia, PF, Pappo, AS, Altman, J, Bhatia, S, Borinstein, SC, Flynn, J, Frazier, AL, George, S, Goldsby, R, Hayashi, R, Huang, MS, Johnson, RH, Beaupin, LK, Link, MP, Oeffinger, KC, Orr, KM, Reed, D, Spraker, HL, Thomas, DA, von Mehren, M, Wechsler, DS, Whelan, KF, Zebrack, B, Shead, DA, and Sundar, H. "Adolescent and young adult oncology, version 2.2014." Journal of the National Comprehensive Cancer Network : JNCCN 12.1 (January 2014): 21-32.
PMID
24453290
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
12
Issue
1
Publish Date
2014
Start Page
21
End Page
32
DOI
10.6004/jnccn.2014.0004

N-Myc differentially regulates expression of MXI1 isoforms in neuroblastoma.

Amplification of the MYCN proto-oncogene is associated with a poor prognosis in patients with metastatic neuroblastoma (NB). MYCN encodes the N-Myc protein, a transcriptional regulator that dimerizes with the Max transcription factor, binds to E-box DNA sequences, and regulates genes involved in cell growth and apoptosis. Overexpression of N-Myc leads to transcriptional activation and an increase in NB cell proliferation. Mxi1, a member of the Myc family of transcriptional regulators, also binds to Max. However, Mxi1 is a transcriptional repressor and inhibits proliferation of NB cells, suggesting that Mxi1 functions as an N-Myc antagonist. Our laboratory previously identified Mxi1-0, an alternatively transcribed Mxi1 isoform. Mxi1-0 has properties distinct from those of Mxi1; in contrast to Mxi1, Mxi1-0 is unable to suppress c-Myc-dependent transcription. We now show that Mxi1-0 expression increases in response to MYCN overexpression in NB cells, with a positive correlation between MYCN and MXI1-0 RNA levels. We also show that N-Myc expression differentially regulates the MXI1 and MXI1-0 promoters: Increased MYCN expression suppresses MXI1 promoter activity while enhancing transcription through the MXI1-0 promoter. Finally, induction of Mxi1-0 leads to increased proliferation, whereas expression of Mxi1 inhibits cell growth, indicating differential roles for these two proteins. These data suggest that N-Myc differentially regulates the expression of MXI1 and MXI1-0 and can alter the balance between the two transcription factors. Furthermore, MXI1-0 appears to be a downstream target of MYCN-dependent signaling pathways and may contribute to N-Myc-dependent cell growth and proliferation.

Authors
Armstrong, MB; Mody, RJ; Ellis, DC; Hill, AB; Erichsen, DA; Wechsler, DS
MLA Citation
Armstrong, MB, Mody, RJ, Ellis, DC, Hill, AB, Erichsen, DA, and Wechsler, DS. "N-Myc differentially regulates expression of MXI1 isoforms in neuroblastoma." Neoplasia (New York, N.Y.) 15.12 (December 2013): 1363-1370.
PMID
24403858
Source
epmc
Published In
Neoplasia (New York, N.Y.)
Volume
15
Issue
12
Publish Date
2013
Start Page
1363
End Page
1370
DOI
10.1593/neo.11606

Iron deprivation in cancer--potential therapeutic implications.

Iron is essential for normal cellular function. It participates in a wide variety of cellular processes, including cellular respiration, DNA synthesis, and macromolecule biosynthesis. Iron is required for cell growth and proliferation, and changes in intracellular iron availability can have significant effects on cell cycle regulation, cellular metabolism, and cell division. Perhaps not surprisingly then, neoplastic cells have been found to have higher iron requirements than normal, non-malignant cells. Iron depletion through chelation has been explored as a possible therapeutic intervention in a variety of cancers. Here, we will review iron homeostasis in non-malignant and malignant cells, the widespread effects of iron depletion on the cell, the various iron chelators that have been explored in the treatment of cancer, and the tumor types that have been most commonly studied in the context of iron chelation.

Authors
Heath, JL; Weiss, JM; Lavau, CP; Wechsler, DS
MLA Citation
Heath, JL, Weiss, JM, Lavau, CP, and Wechsler, DS. "Iron deprivation in cancer--potential therapeutic implications. (Published online)" Nutrients 5.8 (July 24, 2013): 2836-2859. (Review)
PMID
23887041
Source
pubmed
Published In
Nutrients
Volume
5
Issue
8
Publish Date
2013
Start Page
2836
End Page
2859
DOI
10.3390/nu5082836

A CALM-derived nuclear export signal is essential for CALM-AF10-mediated leukemogenesis.

The t(10;11) chromosomal translocation gives rise to the CALM-AF10 fusion gene and is found in patients with aggressive and difficult-to-treat hematopoietic malignancies. CALM-AF10-driven leukemias are characterized by HOXA gene up-regulation and a global reduction in H3K79 methylation. DOT1L, the H3K79 methyltransferase, interacts with the octapeptide/leucine zipper domain of AF10, and this region has been shown to be necessary and sufficient for CALM-AF10-mediated transformation. However, the precise role of CALM in leukemogenesis remains unclear. Here, we show that CALM contains a nuclear export signal (NES) that mediates cytoplasmic localization of CALM-AF10 and is necessary for CALM-AF10-dependent transformation. Fusions of the CALM NES (NES(CALM)-AF10) or NES motifs from heterologous proteins (ABL1, Rev, PKIA, APC) in-frame with AF10 are sufficient to immortalize murine hematopoietic progenitors in vitro. The CALM NES is essential for CALM-AF10-dependent Hoxa gene up-regulation and aberrant H3K79 methylation, possibly by mislocalization of DOT1L. Finally, we observed that CALM-AF10 leukemia cells are selectively sensitive to inhibition of nuclear export by Leptomycin B. These findings uncover a novel mechanism of leukemogenesis mediated by the nuclear export pathway and support further investigation of the utility of nuclear export inhibitors as therapeutic agents for patients with CALM-AF10 leukemias.

Authors
Conway, AE; Scotland, PB; Lavau, CP; Wechsler, DS
MLA Citation
Conway, AE, Scotland, PB, Lavau, CP, and Wechsler, DS. "A CALM-derived nuclear export signal is essential for CALM-AF10-mediated leukemogenesis." Blood 121.23 (June 6, 2013): 4758-4768.
PMID
23487024
Source
pubmed
Published In
Blood
Volume
121
Issue
23
Publish Date
2013
Start Page
4758
End Page
4768
DOI
10.1182/blood-2012-06-435792

CALM-AF10 LEUKEMIA CELL PROLIFERATION IS IMPAIRED BY IRON DEPRIVATION IN VITRO AND IN VIVO

Authors
Heath, J; Lavau, C; Weiss, J; Scotland, P; Wechsler, D
MLA Citation
Heath, J, Lavau, C, Weiss, J, Scotland, P, and Wechsler, D. "CALM-AF10 LEUKEMIA CELL PROLIFERATION IS IMPAIRED BY IRON DEPRIVATION IN VITRO AND IN VIVO." PEDIATRIC BLOOD & CANCER 60 (June 2013): S40-S40.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
60
Publish Date
2013
Start Page
S40
End Page
S40

NUCLEAR EXPORT INHIBITORS REDUCE PROLIFERATION OF CALM-AF10 LEUKEMIA CELLS

Authors
Lilla, SF; Conway, A; Scotland, P; Lavau, C; Wechsler, D
MLA Citation
Lilla, SF, Conway, A, Scotland, P, Lavau, C, and Wechsler, D. "NUCLEAR EXPORT INHIBITORS REDUCE PROLIFERATION OF CALM-AF10 LEUKEMIA CELLS." PEDIATRIC BLOOD & CANCER 60 (June 2013): S41-S42.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
60
Publish Date
2013
Start Page
S41
End Page
S42

THE ROLES OF MXI1 AND MXI0 IN N-MYC-MEDIATED NEUROBLASTOMA TUMOR PATHOGENESIS

Authors
Armstrong, M; Ellis, DC; Wechsler, D
MLA Citation
Armstrong, M, Ellis, DC, and Wechsler, D. "THE ROLES OF MXI1 AND MXI0 IN N-MYC-MEDIATED NEUROBLASTOMA TUMOR PATHOGENESIS." PEDIATRIC BLOOD & CANCER 60 (June 2013): S65-S65.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
60
Publish Date
2013
Start Page
S65
End Page
S65

High motility group overexpression accelerates T-cell leukemogenesis

Authors
Heath, JL; Wechsler, DS
MLA Citation
Heath, JL, and Wechsler, DS. "High motility group overexpression accelerates T-cell leukemogenesis." Leukemia and Lymphoma 54.8 (2013): 1577-1578.
PMID
23418894
Source
scival
Published In
Leukemia & Lymphoma (Informa)
Volume
54
Issue
8
Publish Date
2013
Start Page
1577
End Page
1578
DOI
10.3109/10428194.2013.777069

Iron Deprivation Impairs Proliferation of CALM-AF10 leukemia Cells in Vitro and in Vivo

Authors
Heath, JL; Weiss, J; Scotland, PB; Lavau, CP; Wechsler, DS
MLA Citation
Heath, JL, Weiss, J, Scotland, PB, Lavau, CP, and Wechsler, DS. "Iron Deprivation Impairs Proliferation of CALM-AF10 leukemia Cells in Vitro and in Vivo." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Iron Deprivation Impairs Proliferation of CALM-AF10 leukemia Cells in Vitro and in Vivo

Authors
Heath, JL; Weiss, J; Scotland, PB; Lavau, CP; Wechsler, DS
MLA Citation
Heath, JL, Weiss, J, Scotland, PB, Lavau, CP, and Wechsler, DS. "Iron Deprivation Impairs Proliferation of CALM-AF10 leukemia Cells in Vitro and in Vivo." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Adolescent and Young Adult Oncology

Authors
Coccia, PF; Altman, J; Bhatia, S; Borinstein, SC; Flynn, J; George, S; Goldsby, R; Hayashi, R; Huang, MS; Johnson, RH; Beaupin, LK; Link, MP; Oeffinger, KC; Orr, KM; Pappo, AS; Reed, D; Spraker, HL; Thomas, DA; von Mehren, M; Wechsler, DS; Whelan, KF; Zebrack, BJ; Sundar, H; Shead, DA
MLA Citation
Coccia, PF, Altman, J, Bhatia, S, Borinstein, SC, Flynn, J, George, S, Goldsby, R, Hayashi, R, Huang, MS, Johnson, RH, Beaupin, LK, Link, MP, Oeffinger, KC, Orr, KM, Pappo, AS, Reed, D, Spraker, HL, Thomas, DA, von Mehren, M, Wechsler, DS, Whelan, KF, Zebrack, BJ, Sundar, H, and Shead, DA. "Adolescent and Young Adult Oncology." Journal of the National Comprehensive Cancer Network 10.9 (September 2012): 1112-1150.
Source
crossref
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
9
Publish Date
2012
Start Page
1112
End Page
1150
DOI
10.6004/jnccn.2012.0117

IRON DEPRIVATION IMPAIRS PROLIFERATION OF CALM-AF10 LEUKEMIA IN VITRO AND IN VIVO

Authors
Heath, J; Lavau, C; Scotland, P; Wechsler, D
MLA Citation
Heath, J, Lavau, C, Scotland, P, and Wechsler, D. "IRON DEPRIVATION IMPAIRS PROLIFERATION OF CALM-AF10 LEUKEMIA IN VITRO AND IN VIVO." PEDIATRIC BLOOD & CANCER 58.7 (July 2012): 1039-1039.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
58
Issue
7
Publish Date
2012
Start Page
1039
End Page
1039

MXI1 AND N-MYC INDUCE NEUROBLASTOMA CELL APOPTOSIS VIA DISTINCT PATHWAYS

Authors
Armstrong, M; Hill, A; Wechsler, D
MLA Citation
Armstrong, M, Hill, A, and Wechsler, D. "MXI1 AND N-MYC INDUCE NEUROBLASTOMA CELL APOPTOSIS VIA DISTINCT PATHWAYS." PEDIATRIC BLOOD & CANCER 58.7 (July 2012): 1077-1077.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
58
Issue
7
Publish Date
2012
Start Page
1077
End Page
1077

Successful treatment of disseminated cryptococcal infection in a pediatric acute lymphoblastic leukemia patient during induction.

Disseminated cryptococcal infection is rarely reported in the setting of pediatric acute leukemia, despite the immunocompromised state of these patients. However, when present, disseminated cryptococcal infection poses treatment challenges and is associated with significant morbidity and mortality. Treatment of invasive fungal disease in a child with acute leukemia requires a delicate balance between antifungal and antineoplastic therapy. This balance is particularly important early in the course of leukemia, as both the underlying disease and overwhelming infection can be life threatening. We describe the successful management of life-threatening disseminated cryptococcosis in a child with acute lymphoblastic leukemia during induction therapy.

Authors
Heath, JL; Yin, DE; Wechsler, DS; Turner, DA
MLA Citation
Heath, JL, Yin, DE, Wechsler, DS, and Turner, DA. "Successful treatment of disseminated cryptococcal infection in a pediatric acute lymphoblastic leukemia patient during induction." J Pediatr Hematol Oncol 34.4 (May 2012): e161-e163.
PMID
22258349
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
34
Issue
4
Publish Date
2012
Start Page
e161
End Page
e163
DOI
10.1097/MPH.0b013e318236c502

Abstract LB-154: Nuclear export of CALM-AF10 is essential for leukemogenesis

Authors
Conway, AE; Scotland, PB; Lavau, CP; Wechsler, DS
MLA Citation
Conway, AE, Scotland, PB, Lavau, CP, and Wechsler, DS. "Abstract LB-154: Nuclear export of CALM-AF10 is essential for leukemogenesis." Cancer Research 72.8 Supplement (April 15, 2012): LB-154-LB-154.
Source
crossref
Published In
Cancer Research
Volume
72
Issue
8 Supplement
Publish Date
2012
Start Page
LB-154
End Page
LB-154
DOI
10.1158/1538-7445.AM2012-LB-154

MLL duplication in a pediatric patient with B-cell lymphoblastic lymphoma.

Lymphoblastic lymphoma is the second most common type of non-Hodgkin lymphoma seen in children. Approximately, 90% of lymphoblastic lymphomas arise from T cells, with the remaining 10% being B-cell-lineage derived. Although T-cell lymphoblastic lymphoma most frequently occurs in the anterior mediastinum (thymus), B-cell lymphoblastic lymphoma (B-LBL) predominates in extranodal sites such as skin and bone. Here, we describe a pediatric B-LBL patient who presented with extensive abdominal involvement and whose lymphoma cells displayed segmental duplication of the mixed lineage leukemia (MLL) gene. MLL duplication/amplification has been described primarily in acute myeloid leukemia and myelodysplastic syndrome with no published reports of discrete MLL duplication/amplification events in B-LBL. The MLL gene duplication noted in this case may represent a novel mechanism for tumorigenesis in B-LBL.

Authors
Mater, DV; Goodman, BK; Wang, E; Gaca, AM; Wechsler, DS
MLA Citation
Mater, DV, Goodman, BK, Wang, E, Gaca, AM, and Wechsler, DS. "MLL duplication in a pediatric patient with B-cell lymphoblastic lymphoma." J Pediatr Hematol Oncol 34.3 (April 2012): e120-e123.
PMID
22052166
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
34
Issue
3
Publish Date
2012
Start Page
e120
End Page
e123
DOI
10.1097/MPH.0b013e3182273b57

Adolescent and young adult oncology clinical practice guidelines in oncology

Cancer is the leading cause of death among the adolescent and young adult (AYA) population, excluding homicide, suicide, or unintentional injury. AYA patients should be managed by a multidisciplinary team of health care professionals who are well-versed in the specific developmental issues relevant to this patient population. The recommendations for age-appropriate care outlined in these NCCN Guidelines include psychosocial assessment, a discussion of infertility risks associated with treatment and options for fertility preservation, genetic and familial risk assessment for all patients after diagnosis, screening and monitoring of late effects in AYA cancer survivors after successful completion of therapy, and palliative care and end-of-life considerations for patients for whom curative therapy fails. © JNCCN - Journal of the National Comprehensive Cancer Network.

Authors
Coccia, PF; Altman, J; Bhatia, S; Borinstein, SC; Flynn, J; George, S; Goldsby, R; Hayashi, R; Huang, MS; Johnson, RH; Beaupin, LK; Link, MP; Oeffinger, KC; Orr, KM; Pappo, AS; Reed, D; Spraker, HL; Thomas, DA; Mehren, MV; Wechsler, DS; Whelan, KF; Zebrack, B; Sundar, H; Shead, DA
MLA Citation
Coccia, PF, Altman, J, Bhatia, S, Borinstein, SC, Flynn, J, George, S, Goldsby, R, Hayashi, R, Huang, MS, Johnson, RH, Beaupin, LK, Link, MP, Oeffinger, KC, Orr, KM, Pappo, AS, Reed, D, Spraker, HL, Thomas, DA, Mehren, MV, Wechsler, DS, Whelan, KF, Zebrack, B, Sundar, H, and Shead, DA. "Adolescent and young adult oncology clinical practice guidelines in oncology." JNCCN Journal of the National Comprehensive Cancer Network 10.9 (2012): 1112-1150.
PMID
22956810
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
10
Issue
9
Publish Date
2012
Start Page
1112
End Page
1150

The PICALM protein plays a key role in iron homeostasis and cell proliferation.

The ubiquitously expressed phosphatidylinositol binding clathrin assembly (PICALM) protein associates with the plasma membrane, binds clathrin, and plays a role in clathrin-mediated endocytosis. Alterations of the human PICALM gene are present in aggressive hematopoietic malignancies, and genome-wide association studies have recently linked the PICALM locus to late-onset Alzheimer's disease. Inactivating and hypomorphic Picalm mutations in mice cause different degrees of severity of anemia, abnormal iron metabolism, growth retardation and shortened lifespan. To understand PICALM's function, we studied the consequences of PICALM overexpression and characterized PICALM-deficient cells derived from mutant fit1 mice. Our results identify a role for PICALM in transferrin receptor (TfR) internalization and demonstrate that the C-terminal PICALM residues are critical for its association with clathrin and for the inhibitory effect of PICALM overexpression on TfR internalization. Murine embryonic fibroblasts (MEFs) that are deficient in PICALM display several characteristics of iron deficiency (increased surface TfR expression, decreased intracellular iron levels, and reduced cellular proliferation), all of which are rescued by retroviral PICALM expression. The proliferation defect of cells that lack PICALM results, at least in part, from insufficient iron uptake, since it can be corrected by iron supplementation. Moreover, PICALM-deficient cells are particularly sensitive to iron chelation. Taken together, these data reveal that PICALM plays a critical role in iron homeostasis, and offer new perspectives into the pathogenesis of PICALM-associated diseases.

Authors
Scotland, PB; Heath, JL; Conway, AE; Porter, NB; Armstrong, MB; Walker, JA; Klebig, ML; Lavau, CP; Wechsler, DS
MLA Citation
Scotland, PB, Heath, JL, Conway, AE, Porter, NB, Armstrong, MB, Walker, JA, Klebig, ML, Lavau, CP, and Wechsler, DS. "The PICALM protein plays a key role in iron homeostasis and cell proliferation." PLoS One 7.8 (2012): e44252-.
PMID
22952941
Source
pubmed
Published In
PloS one
Volume
7
Issue
8
Publish Date
2012
Start Page
e44252
DOI
10.1371/journal.pone.0044252

WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4

WHIM syndrome is a rare, autosomal dominant, immunodeficiency disorder sonamed because it is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis (defective neutrophil egress from the BM). Gain-offunction mutations that truncate the C-terminus of the chemokine receptor CXCR4 by 10-19 amino acids cause WHIM syndrome. We have identified a family with autosomal dominant inheritance of WHIM syndrome that is caused by a missense mutation in CXCR4, E343K (1027G → A). This mutation is also located in the C-terminal domain, a region responsible for negative regulation of the receptor. Accordingly, like CXCR4R334X, the most common truncation mutation in WHIM syndrome, CXCR4 E343K mediated approximately 2-fold increased signaling in calcium flux and chemotaxis assays relative to wild-type CXCR4; however, CXCR4 E343K had a reduced effect on blocking normal receptor down-regulation from the cell surface. Therefore, in addition to truncating mutations in the C-terminal domain of CXCR4, WHIM syndrome may be caused by a single charge-changing amino acid substitution in this domain, E343K, that results in increased receptor signaling.

Authors
Liu, Q; Chen, H; Ojode, T; Gao, X; Anaya-O'Brien, S; Turner, NA; Ulrick, J; DeCastro, R; Kelly, C; Cardones, AR; Gold, SH; Hwang, EI; Wechsler, DS; Malech, HL; Murphy, PM; McDermott, DH
MLA Citation
Liu, Q, Chen, H, Ojode, T, Gao, X, Anaya-O'Brien, S, Turner, NA, Ulrick, J, DeCastro, R, Kelly, C, Cardones, AR, Gold, SH, Hwang, EI, Wechsler, DS, Malech, HL, Murphy, PM, and McDermott, DH. "WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4." Blood 120.1 (2012): 181-189.
PMID
22596258
Source
scival
Published In
Blood
Volume
120
Issue
1
Publish Date
2012
Start Page
181
End Page
189
DOI
10.1182/blood-2011-12-395608

CALM Insufficiency Impairs Leukemia Cell Proliferation by Limiting Iron Uptake

Authors
Lavau, CP; Heath, JL; Scotland, PB; Wechsler, DS
MLA Citation
Lavau, CP, Heath, JL, Scotland, PB, and Wechsler, DS. "CALM Insufficiency Impairs Leukemia Cell Proliferation by Limiting Iron Uptake." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
642
End Page
642

MXI1, A MEMBER OF THE MAD PROTEIN FAMILY, ANTAGONIZES N-MYC DEPENDENT APOPTOSIS AND PROLIFERATION IN NEUROBLASTOMA CELLS

Authors
Armstrong, M; Erichsen, D; Wechsler, D
MLA Citation
Armstrong, M, Erichsen, D, and Wechsler, D. "MXI1, A MEMBER OF THE MAD PROTEIN FAMILY, ANTAGONIZES N-MYC DEPENDENT APOPTOSIS AND PROLIFERATION IN NEUROBLASTOMA CELLS." PEDIATRIC BLOOD & CANCER 56.6 (June 2011): 960-960.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
56
Issue
6
Publish Date
2011
Start Page
960
End Page
960

PERTURBED IRON METABOLISM IN CALM-DEFICIENT CELLS

Authors
Heath, J; Scotland, P; Walker, J; Lavau, C; Wechsler, D
MLA Citation
Heath, J, Scotland, P, Walker, J, Lavau, C, and Wechsler, D. "PERTURBED IRON METABOLISM IN CALM-DEFICIENT CELLS." PEDIATRIC BLOOD & CANCER 56.6 (June 2011): 921-921.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
56
Issue
6
Publish Date
2011
Start Page
921
End Page
921

Synchronous occurrence of metastatic Wilms tumor and ganglioneuroma.

We describe a 4-year-old female patient with a persistent paraspinal mass following chemotherapy for Wilms tumor. A discordant response to chemotherapy prompted biopsy of the persistent mass, which revealed a ganglioneuroma. This report highlights the synchronous occurrence of different tumors in the same patient, and suggests that repeat biopsies should be considered when contiguous tumor masses do not respond as expected.

Authors
Moran, C; Greiner, RJ; Mardam-Bey, SW; Hollingsworth, CL; Kulbacki, E; Wechsler, DS
MLA Citation
Moran, C, Greiner, RJ, Mardam-Bey, SW, Hollingsworth, CL, Kulbacki, E, and Wechsler, DS. "Synchronous occurrence of metastatic Wilms tumor and ganglioneuroma." Pediatr Blood Cancer 55.3 (September 2010): 562-565.
PMID
20658632
Source
pubmed
Published In
Pediatric Blood & Cancer
Volume
55
Issue
3
Publish Date
2010
Start Page
562
End Page
565
DOI
10.1002/pbc.22553

CALM DEFICIENCY ALTERS EXPRESSION AND ENDOCYTOSIS OF GROWTH FACTOR RECEPTORS

Authors
Wechsler, D; Scotland, P; Conway, A; Lavau, C
MLA Citation
Wechsler, D, Scotland, P, Conway, A, and Lavau, C. "CALM DEFICIENCY ALTERS EXPRESSION AND ENDOCYTOSIS OF GROWTH FACTOR RECEPTORS." PEDIATRIC BLOOD & CANCER 54.6 (June 2010): 817-817.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
54
Issue
6
Publish Date
2010
Start Page
817
End Page
817

Abstract 3952: CALM deficiency in fit1 embryonic cells alters expression and rate of endocytosis of growth factor receptors

Authors
Scotland, PB; Lavau, CP; Conway, AE; Wechsler, DS
MLA Citation
Scotland, PB, Lavau, CP, Conway, AE, and Wechsler, DS. "Abstract 3952: CALM deficiency in fit1 embryonic cells alters expression and rate of endocytosis of growth factor receptors." Cancer Research 70.8 Supplement (April 15, 2010): 3952-3952.
Source
crossref
Published In
Cancer Research
Volume
70
Issue
8 Supplement
Publish Date
2010
Start Page
3952
End Page
3952
DOI
10.1158/1538-7445.AM10-3952

(POSTER 151) MECHANISMS OF CALM-DEPENDENT LEUKEMOGENESIS: CALM FUSION PROTEINS UPREGULATE EXPRESSION OF THE IL-3 GROWTH FACTOR RECEPTOR

Authors
Walker, JA; Wechsler, DS; Lavau, CP
MLA Citation
Walker, JA, Wechsler, DS, and Lavau, CP. "(POSTER 151) MECHANISMS OF CALM-DEPENDENT LEUKEMOGENESIS: CALM FUSION PROTEINS UPREGULATE EXPRESSION OF THE IL-3 GROWTH FACTOR RECEPTOR." PEDIATRIC BLOOD & CANCER 52.6 (June 2009): 715-716.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
52
Issue
6
Publish Date
2009
Start Page
715
End Page
716

MECHANISMS OF CALM-DEPENDENT ACUTE MYELOID LEUKEMOGENESIS: DEVELOPMENT OF CALM-INDUCIBLE CELL LINES

Authors
Greiner, RJ; Goldstein, SA; Scotland, PB; Lavau, CP; Wechsler, DS
MLA Citation
Greiner, RJ, Goldstein, SA, Scotland, PB, Lavau, CP, and Wechsler, DS. "MECHANISMS OF CALM-DEPENDENT ACUTE MYELOID LEUKEMOGENESIS: DEVELOPMENT OF CALM-INDUCIBLE CELL LINES." PEDIATRIC BLOOD & CANCER 52.6 (June 2009): 722-722.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
52
Issue
6
Publish Date
2009
Start Page
722
End Page
722

DISSECTING THE ROLE OF CALM IN LEUKEMOGENESIS: ELUCIDATION OF FUNCTIONAL DOMAINS REQUIRED FOR CLATHRIN-DEPENDENT ENDOCYTOSIS

Authors
Scotland, PB; Conway, AE; Brooks, NL; Lavau, CP; Wechsler, DS
MLA Citation
Scotland, PB, Conway, AE, Brooks, NL, Lavau, CP, and Wechsler, DS. "DISSECTING THE ROLE OF CALM IN LEUKEMOGENESIS: ELUCIDATION OF FUNCTIONAL DOMAINS REQUIRED FOR CLATHRIN-DEPENDENT ENDOCYTOSIS." PEDIATRIC BLOOD & CANCER 52.6 (June 2009): 714-715.
Source
wos-lite
Published In
Pediatric Blood & Cancer
Volume
52
Issue
6
Publish Date
2009
Start Page
714
End Page
715

Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome.

We hypothesized that sirolimus, an mTOR inhibitor, may be effective in patients with autoimmune lymphoproliferative syndrome (ALPS) and treated patients who were intolerant to or failed other therapies. Four patients were treated for autoimmune cytopenias; all had a rapid complete or near complete response. Two patients were treated for autoimmune arthritis and colitis, demonstrating marked improvement. Three patients had complete resolution of lymphadenopathy and splenomegaly and all patients had a reduction in double negative T cells, a population hallmark of the disease. Based on these significant responses, we recommend that sirolimus be considered as second-line therapy for patients with steroid-refractory disease.

Authors
Teachey, DT; Greiner, R; Seif, A; Attiyeh, E; Bleesing, J; Choi, J; Manno, C; Rappaport, E; Schwabe, D; Sheen, C; Sullivan, KE; Zhuang, H; Wechsler, DS; Grupp, SA
MLA Citation
Teachey, DT, Greiner, R, Seif, A, Attiyeh, E, Bleesing, J, Choi, J, Manno, C, Rappaport, E, Schwabe, D, Sheen, C, Sullivan, KE, Zhuang, H, Wechsler, DS, and Grupp, SA. "Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome." Br J Haematol 145.1 (April 2009): 101-106.
PMID
19208097
Source
pubmed
Published In
British Journal of Haematology
Volume
145
Issue
1
Publish Date
2009
Start Page
101
End Page
106
DOI
10.1111/j.1365-2141.2009.07595.x

Complete Responses in Patients with Autoimmune Lymphoproliferative Syndrome (ALPS) Using the mTOR Inhibitor Sirolimus (rapamycin).

Authors
Teachey, DT; Greiner, RJ; Schwabe, D; Bleesing, J; Manno, CS; Sullivan, K; Wechsler, DS; Grupp, SA
MLA Citation
Teachey, DT, Greiner, RJ, Schwabe, D, Bleesing, J, Manno, CS, Sullivan, K, Wechsler, DS, and Grupp, SA. "Complete Responses in Patients with Autoimmune Lymphoproliferative Syndrome (ALPS) Using the mTOR Inhibitor Sirolimus (rapamycin)." November 16, 2008.
Source
wos-lite
Published In
Blood
Volume
112
Issue
11
Publish Date
2008
Start Page
891
End Page
892

Perturbed endocytosis as a mechanism of CALM-dependent leukemogenesis: Identification of specific CALM domains required for internalization and demonstration of prolonged JAK2 signaling in response to GM-CSF

Authors
Brooks, NL; Erichsen, DA; Wechsler, DS
MLA Citation
Brooks, NL, Erichsen, DA, and Wechsler, DS. "Perturbed endocytosis as a mechanism of CALM-dependent leukemogenesis: Identification of specific CALM domains required for internalization and demonstration of prolonged JAK2 signaling in response to GM-CSF." November 16, 2007.
Source
wos-lite
Published In
Blood
Volume
110
Issue
11
Publish Date
2007
Start Page
538A
End Page
538A

Consensus on a core curriculum in American training programs in pediatric hematology-oncology: a report from the ASPHO Training Committee.

The Training Committee (TC) of the American Society of Pediatric Hematology/Oncology created a foundation of common goals and objectives that could provide a structure for fellowship programs. The TC conducted a survey of program directors for input into the structure of their programs and training methods and the results are presented here. Additionally, a suggested core program is outlined, taking into account the new common requirements as stipulated by the ACGME and ABP, and additional suggestions from the program directors. This paper highlights the suggested training objectives and educational opportunities that should be afforded all fellows in this sub-specialty. The goal of this consensus statement is to provide a model curriculum to improve quality and consistency of training and achieve compliance with new requirements while simultaneously recognizing the importance of alternative approaches that emphasize each program's unique strengths and character.

Authors
Hastings, C; Wechsler, DS; Stine, KC; Graham, DK; Abshire, T
MLA Citation
Hastings, C, Wechsler, DS, Stine, KC, Graham, DK, and Abshire, T. "Consensus on a core curriculum in American training programs in pediatric hematology-oncology: a report from the ASPHO Training Committee." Pediatr Hematol Oncol 24.7 (October 2007): 503-512.
PMID
17786786
Source
pubmed
Published In
Pediatric Hematology-Oncology (Informa)
Volume
24
Issue
7
Publish Date
2007
Start Page
503
End Page
512
DOI
10.1080/08880010701533645

Perturbed endocytosis by leukemogenic CALM-containing fusion proteins is associated with prolonged growth factor signaling and enhanced cellular proliferation.

Authors
Chao, MM; Erichsen, DA; Krajewski, ML; Bohlander, SK; Wechsler, DS
MLA Citation
Chao, MM, Erichsen, DA, Krajewski, ML, Bohlander, SK, and Wechsler, DS. "Perturbed endocytosis by leukemogenic CALM-containing fusion proteins is associated with prolonged growth factor signaling and enhanced cellular proliferation." November 16, 2005.
Source
wos-lite
Published In
Blood
Volume
106
Issue
11
Publish Date
2005
Start Page
696A
End Page
696A

Burkitt lymphoma in a child with osteogenesis imperfecta.

Authors
Choi, SW; Wechsler, DS
MLA Citation
Choi, SW, and Wechsler, DS. "Burkitt lymphoma in a child with osteogenesis imperfecta." Pediatr Blood Cancer 45.6 (November 2005): 863-864. (Letter)
PMID
15926161
Source
pubmed
Published In
Pediatric Blood & Cancer
Volume
45
Issue
6
Publish Date
2005
Start Page
863
End Page
864
DOI
10.1002/pbc.20439

Early diagnosis remains the most reliable way to cure chidren with melanoma: Response

Authors
Chao, MM; Wechsler, DS
MLA Citation
Chao, MM, and Wechsler, DS. "Early diagnosis remains the most reliable way to cure chidren with melanoma: Response." Pediatric Blood & Cancer 45.3 (September 2005): 356-356.
Source
crossref
Published In
Pediatric Blood & Cancer
Volume
45
Issue
3
Publish Date
2005
Start Page
356
End Page
356
DOI
10.1002/pbc.20398

Aortobronchial fistula in a pediatric patient with massive hemoptysis: treatment by means of an aortic endograft.

We present an 11-year-old girl with acute myelogenous leukemia and hemoptysis from abscess erosion into the descending thoracic aorta. We report a pediatric case of an aortobronchial fistula treated with an aortic endograft and discuss the technical limitations and potential complications of this procedure.

Authors
Khare, RK; Settimi, PD; Mba, NI; Wechsler, DS; Bratton, SL; Williams, DM
MLA Citation
Khare, RK, Settimi, PD, Mba, NI, Wechsler, DS, Bratton, SL, and Williams, DM. "Aortobronchial fistula in a pediatric patient with massive hemoptysis: treatment by means of an aortic endograft." Ann Thorac Surg 80.2 (August 2005): 731-733.
PMID
16039247
Source
pubmed
Published In
Annals of Thoracic Surgery
Volume
80
Issue
2
Publish Date
2005
Start Page
731
End Page
733
DOI
10.1016/j.athoracsur.2004.02.045

Testicular chloroma in a nonleukemic infant.

Extramedullary myeloid cell tumors (EMCT) are localized collections of immature myeloid cells that occur outside of the bone marrow. Usually observed concurrently with bone marrow disease, EMCT also may occur in the absence of overt marrow leukemia. In this report, we describe an infant with a testicular mass that was identified as an EMCT after orchiectomy. Unlike the only previously reported case of infantile testicular chloroma, this patient did not exhibit bone marrow disease at diagnosis. Because systemic chemotherapy is considered to be superior to local control (surgery, radiation therapy), the patient was treated with intensively timed induction chemotherapy followed by 3 cycles of maintenance treatment (according to CCG protocol #2891) but no radiation therapy. The patient remains disease-free 18 months after diagnosis.

Authors
Armstrong, MB; Nafiu, OO; Valdez, R; Park, JM; Williams, JA; Wechsler, DS
MLA Citation
Armstrong, MB, Nafiu, OO, Valdez, R, Park, JM, Williams, JA, and Wechsler, DS. "Testicular chloroma in a nonleukemic infant." J Pediatr Hematol Oncol 27.7 (July 2005): 393-396.
PMID
16012331
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
27
Issue
7
Publish Date
2005
Start Page
393
End Page
396

High-risk surgically resected pediatric melanoma and adjuvant interferon therapy.

BACKGROUND: Pediatric patients with high-risk surgically resected melanoma are at risk for relapse, yet little is known about these young patients and how they tolerate high-dose interferon therapy. PROCEDURE: We reviewed medical records of patients (< or =18 years) with high-risk melanoma referred to the University of Michigan Pediatric Hematology-Oncology service between January 1989 and July 2003. RESULTS: Fourteen patients were identified with high-risk resected melanoma. The median age at diagnosis was 8.5 years. The median time to establish diagnosis was 9 months. Primary lesions were diagnosed as unequivocal melanoma, atypical epithelioid melanocytic proliferations, or atypical Spitz tumor with indeterminate malignant potential. Twelve patients had a positive sentinel lymph node (SLN) biopsy or a palpable regional lymph node and underwent regional lymph node dissection (LND). Two patients with unequivocal melanoma with Breslow depth >4 mm had negative SLN biopsies. Twelve patients received adjuvant high-dose interferon. The following toxicities were observed: constitutional symptoms, gastrointestinal symptoms, depression or neuropsychiatric symptoms, myelosuppression, elevated AST or ALT, hypothyroidism, and hypertension. Grade 3 or 4 toxicities were uncommon with exception of neutropenia, resulting in modification of therapy in one patient. All patients are alive and free of disease at follow-up (median 24.5 months). CONCLUSIONS: Invasive melanoma can occur in very young children. Despite early signs of malignancy, there is often a delay in diagnosis. Histologically, diagnosis may be difficult because of overlap with Spitz nevi. Pediatric patients tolerated adjuvant high-dose interferon well and may be less likely than adults to require therapy modification secondary to toxicities.

Authors
Chao, MM; Schwartz, JL; Wechsler, DS; Thornburg, CD; Griffith, KA; Williams, JA
MLA Citation
Chao, MM, Schwartz, JL, Wechsler, DS, Thornburg, CD, Griffith, KA, and Williams, JA. "High-risk surgically resected pediatric melanoma and adjuvant interferon therapy." Pediatr Blood Cancer 44.5 (May 2005): 441-448.
PMID
15468307
Source
pubmed
Published In
Pediatric Blood & Cancer
Volume
44
Issue
5
Publish Date
2005
Start Page
441
End Page
448
DOI
10.1002/pbc.20168

Mechanisms of leukemic transformation by MLL-CALM: Identification of a CALM-derived transcriptional regulatory domain

Authors
Fox, EJ; Chao, MM; Wechsler, D
MLA Citation
Fox, EJ, Chao, MM, and Wechsler, D. "Mechanisms of leukemic transformation by MLL-CALM: Identification of a CALM-derived transcriptional regulatory domain." March 4, 2005.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
19
Issue
4
Publish Date
2005
Start Page
A875
End Page
A875

Utility of cranial boost in addition to total body irradiation in the treatment of high risk acute lymphoblastic leukemia

Purpose: Total body irradiation (TBI) as part of a conditioning regimen before hematopoietic stem cell transplant (HSCT) is an important component in the management of acute lymphoblastic leukemia (ALL) that has relapsed or has other certain high-risk features. Controversy exists, however, as to whether a cranial boost in addition to TBI is necessary to prevent central nervous system (CNS) recurrences in these high-risk cases. Previous national trials have included a cranial boost in the absence of data to justify its use. Therefore, the aim of this study was to assess risk of CNS recurrence in ALL patients treated with TBI, to identify subsets of these high-risk patients at an increased or decreased risk of CNS recurrence after TBI, and to investigate whether regimens with higher doses of cranial irradiation further reduce the risk of CNS recurrence. Methods and Materials: Charts of 67 consecutively treated patients with ALL who received TBI before HSCT were reviewed. Data including patient demographics, clinical features at presentation, conditioning regimen, donor source, use of a cranial boost, remission stage at transplant, histologic subtype, cytogenetics, and extramedullary site of presentation were retrospectively collected and correlated with the risk of subsequent CNS recurrence. Results: At the time of analysis, 30 (45%) patients were alive with no evidence of disease, 8 (12%) were alive with recurrence of leukemia, 7 (10.5%) had recurrent ALL but with successful salvage, 7 (11%) died subsequent to recurrence, 14 (21%) died from complications related to HCST, and 1 patient was lost to follow-up (1.5%). Of the patients who recurred after HSCT, the relapses were hematologic in 13 (57%), CNS with or without simultaneous marrow involvement in 3 (13%), and other sites in 7 (30%). Forty-one (61%) patients did not receive an extracranial boost of irradiation with TBI. Two of these patients (4.9%) suffered CNS failures compared with 1 of 26 (3.8%) who received a cranial boost (p = 0.84). None of the 40 patients who presented only with hematologic disease developed a CNS recurrence despite the fact that only 13 of 40 of these patients received a cranial boost after TBI. Cranial boost was therefore not associated with a reduction in CNS recurrence, especially in patients with only hematologic disease at presentation for which there were no failures regardless of the use of additional cranial radiotherapy. Conclusions: Patients who present with hematologic disease only at the time of HSCT have a low risk of CNS recurrence after TBI regardless of the use of a cranial boost, suggesting that a cranial boost may not be necessary in these patients. © 2005 Elsevier Inc.

Authors
Alexander, BM; Wechsler, D; Braun, TM; Levine, J; Herman, J; Yanik, G; Hutchinson, R; Pierce, LJ
MLA Citation
Alexander, BM, Wechsler, D, Braun, TM, Levine, J, Herman, J, Yanik, G, Hutchinson, R, and Pierce, LJ. "Utility of cranial boost in addition to total body irradiation in the treatment of high risk acute lymphoblastic leukemia." International Journal of Radiation Oncology Biology Physics 63.4 (2005): 1191-1196.
PMID
15978741
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
63
Issue
4
Publish Date
2005
Start Page
1191
End Page
1196
DOI
10.1016/j.ijrobp.2005.04.020

Early diagnosis remains the most reliable way to cure children with melanoma [3] (multiple letters)

Authors
Bono, A; Ferrari, A; Chao, MM; Wechsler, DS
MLA Citation
Bono, A, Ferrari, A, Chao, MM, and Wechsler, DS. "Early diagnosis remains the most reliable way to cure children with melanoma [3] (multiple letters)." Pediatric Blood and Cancer 45.3 (2005): 355-356.
PMID
15809990
Source
scival
Published In
Pediatric Blood and Cancer
Volume
45
Issue
3
Publish Date
2005
Start Page
355
End Page
356
DOI
10.1002/pbc.20399

Perturbed endocytosis by CALM-containing fusion proteins: A leukemogenic mechanism in AML.

Authors
Chao, MM; Walker, AC; Pendergast, MB; Bohlander, SK; Wechsler, DS
MLA Citation
Chao, MM, Walker, AC, Pendergast, MB, Bohlander, SK, and Wechsler, DS. "Perturbed endocytosis by CALM-containing fusion proteins: A leukemogenic mechanism in AML." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
922A
End Page
923A

Mechanisms of leukemogenesis by MLL-CALM: Characterization of a CALM-derived transcriptional regulatory domain.

Authors
Chao, MM; Fox, EJ; Wechsler, DS
MLA Citation
Chao, MM, Fox, EJ, and Wechsler, DS. "Mechanisms of leukemogenesis by MLL-CALM: Characterization of a CALM-derived transcriptional regulatory domain." November 16, 2004.
Source
wos-lite
Published In
Blood
Volume
104
Issue
11
Publish Date
2004
Start Page
924A
End Page
924A

Mxi1-0, an alternatively transcribed Mxi1 isoform, is overexpressed in glioblastomas.

The c-Myc transcription factor regulates expression of genes related to cell growth, division, and apoptosis. Mxi1, a member of the Mad family, represses transcription of c-Myc-regulated genes by mediating chromatin condensation via histone deacetylase and the Sin3 corepressor. Mxi1 is a c-Myc antagonist and suppresses cell proliferation in vitro. Here, we describe the identification of Mxi1-0, a novel Mxi1 isoform that is alternatively transcribed from an upstream exon. Mxi1-0 and Mxi1 have different amino-terminal sequences, but share identical Max- and DNA-binding domains. Both isoforms are able to bind Max, to recognize E-box binding sites, and to interact with Sin3. Despite these similarities and in contrast to Mxi1, Mxi1-0 is predominantly localized to the cytoplasm and fails to repress c-Myc-dependent transcription. Although Mxi1-0 and Mxi1 are coexpressed in both human and mouse cells, the relative levels of Mxi1-0 are higher in primary glioblastoma tumors than in normal brain tissue. This variation in the levels of Mxi1-0 and Mxi1 suggests that Mxi1-0 may modulate the Myc-inhibitory activity of Mxi1. The identification of Mxi1-0 as an alternatively transcribed Mxi1 isoform has significant implications for the interpretation of previous Mxi1 studies, particularly those related to the phenotype of the mxi1 knockout mouse.

Authors
Engstrom, LD; Youkilis, AS; Gorelick, JL; Zheng, D; Ackley, V; Petroff, CA; Benson, LQ; Coon, MR; Zhu, X; Hanash, SM; Wechsler, DS
MLA Citation
Engstrom, LD, Youkilis, AS, Gorelick, JL, Zheng, D, Ackley, V, Petroff, CA, Benson, LQ, Coon, MR, Zhu, X, Hanash, SM, and Wechsler, DS. "Mxi1-0, an alternatively transcribed Mxi1 isoform, is overexpressed in glioblastomas." Neoplasia 6.5 (September 2004): 660-673.
PMID
15548375
Source
pubmed
Published In
Neoplasia (New York, N.Y.)
Volume
6
Issue
5
Publish Date
2004
Start Page
660
End Page
673
DOI
10.1593/neo.04244

Metastatic neuroblastoma presenting with binocular blindness from intracranial compression of the optic nerves.

A 2-year-old boy with blindness as an isolated symptom was found to have no light perception binocularly because of compression of both optic nerves by a neuroblastoma infiltrating the walls of the optic canals and medial sphenoid bone. Imaging disclosed a primary tumor near the kidney and multiple osseous metastases. Although neuroblastoma commonly causes blindness by metastasis to the orbit, it rarely causes bilateral blindness from intracranial compression of the optic nerves. This is the first report of bilateral blindness as the presenting feature.

Authors
Lau, JJC; Trobe, JD; Ruiz, RE; Cho, RW; Wechsler, DS; Shah, GV; Gebarski, SS
MLA Citation
Lau, JJC, Trobe, JD, Ruiz, RE, Cho, RW, Wechsler, DS, Shah, GV, and Gebarski, SS. "Metastatic neuroblastoma presenting with binocular blindness from intracranial compression of the optic nerves." J Neuroophthalmol 24.2 (June 2004): 119-124.
PMID
15179064
Source
pubmed
Published In
Journal of Neuro-Ophthalmology
Volume
24
Issue
2
Publish Date
2004
Start Page
119
End Page
124

Mechanisms of leukemic transformation by MLL-CALM: A CALM-derived transcriptional regulatory domain modulates MLL transcriptional activity

Authors
Chao, MM; Walker, AC; Luo, RT; Thirman, MJ; Wechsler, DS
MLA Citation
Chao, MM, Walker, AC, Luo, RT, Thirman, MJ, and Wechsler, DS. "Mechanisms of leukemic transformation by MLL-CALM: A CALM-derived transcriptional regulatory domain modulates MLL transcriptional activity." April 2004.
Source
wos-lite
Published In
Pediatric Research
Volume
55
Issue
4
Publish Date
2004
Start Page
296A
End Page
296A

Differential expression of Mxi0 and MAi1 isoforms in cell differentiation and proliferation

Authors
Zheng, D; Wechsler, DS
MLA Citation
Zheng, D, and Wechsler, DS. "Differential expression of Mxi0 and MAi1 isoforms in cell differentiation and proliferation." April 2004.
Source
wos-lite
Published In
Pediatric Research
Volume
55
Issue
4
Publish Date
2004
Start Page
300A
End Page
300A

Role of cranial boost in addition to total body irradiation in the treatment of high risk acute lymphoblastic leukemia

Authors
Alexander, B; Wechsler, D; Herman, J; Braun, T; Yanik, G; Hutchinson, R; Levine, J; Pierce, L
MLA Citation
Alexander, B, Wechsler, D, Herman, J, Braun, T, Yanik, G, Hutchinson, R, Levine, J, and Pierce, L. "Role of cranial boost in addition to total body irradiation in the treatment of high risk acute lymphoblastic leukemia." 2004.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
60
Issue
1
Publish Date
2004
Start Page
S564
End Page
S564

Subclinical Celiac Disease Presenting as Refractory Iron Deficiency Anemia in Children [2]

Authors
Mody, R; Wechsler, DS
MLA Citation
Mody, R, and Wechsler, DS. "Subclinical Celiac Disease Presenting as Refractory Iron Deficiency Anemia in Children [2]." Journal of Pediatric Hematology/Oncology 26.3 (2004): 154--.
Source
scival
Published In
Journal of Pediatric Hematology/Oncology
Volume
26
Issue
3
Publish Date
2004
Start Page
154-

MLL-CALM inhibits clathrin-dependent endocytosis and confers a growth advantage in FL5.12 cells.

Authors
Chao, MM; Walker, AC; Wechsler, DS
MLA Citation
Chao, MM, Walker, AC, and Wechsler, DS. "MLL-CALM inhibits clathrin-dependent endocytosis and confers a growth advantage in FL5.12 cells." November 16, 2003.
Source
wos-lite
Published In
Blood
Volume
102
Issue
11
Publish Date
2003
Start Page
850A
End Page
850A

Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction.

Diffuse astrocytoma of World Health Organization (WHO) grade II has an inherent tendency to spontaneously progress to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). The molecular basis of astrocytoma progression is still poorly understood, in particular with respect to the progression-associated changes at the mRNA level. Therefore, we compared the transcriptional profile of approximately 6800 genes in primary WHO grade II gliomas and corresponding recurrent high-grade (WHO grade III or IV) gliomas from eight patients using oligonucleotide-based microarray analysis. We identified 66 genes whose mRNA levels differed significantly (P < 0.01, > or =2-fold change) between the primary and recurrent tumors. The microarray data were corroborated by real-time reverse transcription-polymerase chain reaction analysis of 12 selected genes, including 7 genes with increased expression and 5 genes with reduced expression on progression. In addition, the expression of these 12 genes was determined in an independent series of 43 astrocytic gliomas (9 diffuse astrocytomas, 10 anaplastic astrocytomas, 17 primary, and 7 secondary glioblastomas). These analyses confirmed that the transcript levels of nine of the selected genes (COL4A2, FOXM1, MGP, TOP2A, CENPF, IGFBP4, VEGFA, ADD3, and CAMK2G) differed significantly in WHO grade II astrocytomas as compared to anaplastic astrocytomas and/or glioblastomas. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in astrocytoma progression.

Authors
van den Boom, J; Wolter, M; Kuick, R; Misek, DE; Youkilis, AS; Wechsler, DS; Sommer, C; Reifenberger, G; Hanash, SM
MLA Citation
van den Boom, J, Wolter, M, Kuick, R, Misek, DE, Youkilis, AS, Wechsler, DS, Sommer, C, Reifenberger, G, and Hanash, SM. "Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction." Am J Pathol 163.3 (September 2003): 1033-1043.
PMID
12937144
Source
pubmed
Published In
The American journal of pathology
Volume
163
Issue
3
Publish Date
2003
Start Page
1033
End Page
1043
DOI
10.1016/S0002-9440(10)63463-3

Inhibition of endocytosis by MLL-CALM, a novel fusion protein in infant acute myeloid leukemia

Authors
Walker, AC; Chao, MM; Wechsler, DS
MLA Citation
Walker, AC, Chao, MM, and Wechsler, DS. "Inhibition of endocytosis by MLL-CALM, a novel fusion protein in infant acute myeloid leukemia." April 2003.
Source
wos-lite
Published In
Pediatric Research
Volume
53
Issue
4
Publish Date
2003
Start Page
288A
End Page
288A

Refractory iron deficiency anemia as the primary clinical manifestation of celiac disease.

In the absence of dietary insufficiency, iron deficiency is usually caused by chronic blood loss or intestinal malabsorption. Celiac disease is one of the most common causes of intestinal malabsorption during childhood, and its association with insulin-dependent diabetes mellitus has been previously reported. Here the authors describe an otherwise asymptomatic diabetic adolescent boy with iron deficiency anemia that was not responsive to oral iron therapy. A diagnosis of celiac disease was made based on both anti-endomysial antibody titers and small intestinal biopsy. Institution of a gluten-free diet resulted in correction of the anemia. These observations emphasize the importance of considering a diagnosis of celiac disease in patients with nonresponsive iron deficiency anemia, particularly in the setting of insulin-dependent diabetes mellitus.

Authors
Mody, RJ; Brown, PI; Wechsler, DS
MLA Citation
Mody, RJ, Brown, PI, and Wechsler, DS. "Refractory iron deficiency anemia as the primary clinical manifestation of celiac disease." J Pediatr Hematol Oncol 25.2 (February 2003): 169-172.
PMID
12571473
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
25
Issue
2
Publish Date
2003
Start Page
169
End Page
172

A novel chromosomal inversion at 11q23 in infant acute myeloid leukemia fuses MLL to CALM, a gene that encodes a clathrin assembly protein.

Rearrangements involving the MLL gene at chromosome band 11q23 are common in infant acute myeloid leukemias (AMLs). We recently encountered an infant patient with rapidly progressive AML whose leukemic cells harbored a previously undescribed MLL rearrangement involving an inversion of 11q [inv(11)(q14q23)]. We used panhandle PCR to determine that this rearrangement juxtaposed the MLL (Mixed-Lineage Leukemia) gene to the CALM (Clathrin Assembly Lymphoid Myeloid leukemia) gene at 11q14-q21. The CALM protein participates in recruitment of clathrin to internal membrane surfaces, thereby regulating vesicle formation in both endocytosis and intracellular protein transport. Intriguingly, CALM has been identified in other cases of AML as a translocation partner for the AF10 gene, which has independently been found to be an MLL partner in AML. We identified the MLL-CALM fusion transcript (but not the reciprocal CALM-MLL transcript) in leukemia cell RNA by RT-PCR. The predicted 1803 amino acid MLL-CALM fusion protein includes amino-terminal MLL domains involved in transcriptional repression, and carboxy-terminal CALM-derived clathrin-binding domains. The genomic breakpoint in MLL is in the 7th intron (within the breakpoint cluster region); the corresponding CALM breakpoint is in the 7th CALM intron. In contrast, breakpoints in CALM-AF10 translocations lie in the 17th-19th CALM introns (30 kb downstream); also, in these translocations, CALM provides the 5' end of the fusion transcript. Together with its previously recognized association with AF10 in AML, the identification of CALM as an MLL fusion partner suggests that interference with clathrin-mediated trafficking pathways may be an underappreciated mechanism in leukemogenesis.

Authors
Wechsler, DS; Engstrom, LD; Alexander, BM; Motto, DG; Roulston, D
MLA Citation
Wechsler, DS, Engstrom, LD, Alexander, BM, Motto, DG, and Roulston, D. "A novel chromosomal inversion at 11q23 in infant acute myeloid leukemia fuses MLL to CALM, a gene that encodes a clathrin assembly protein." Genes Chromosomes Cancer 36.1 (January 2003): 26-36.
PMID
12461747
Source
pubmed
Published In
Genes, Chromosomes and Cancer
Volume
36
Issue
1
Publish Date
2003
Start Page
26
End Page
36
DOI
10.1002/gcc.10136

Mediastinal seminoma in a patient with Wiskott-Aldrich syndrome.

Shortness of breath developed in an 18-year-old man with Wiskott-Aldrich syndrome, and he was found to have a large mediastinal mass. The gallium scan was positive, and biopsy indicated a seminoma. After treatment with four cycles of chemotherapy, the mass completely resolved. Despite severe thrombocytopenia, he required only two platelet transfusions during therapy. Although lymphomas make up the vast majority of mediastinal tumors in patients with Wiskott-Aldrich syndrome, a positive gallium scan should not preclude the diagnosis of seminoma or the need for confirmatory tissue diagnosis. This report shows the possibility of uneventful and successful treatment of malignancy in a patient with Wiskott-Aldrich syndrome and severe thrombocytopenia.

Authors
Snyder, KM; Rubin, MA; Shulkin, BL; Hutchinson, RJ; Wechsler, DS
MLA Citation
Snyder, KM, Rubin, MA, Shulkin, BL, Hutchinson, RJ, and Wechsler, DS. "Mediastinal seminoma in a patient with Wiskott-Aldrich syndrome." J Pediatr Hematol Oncol 24.8 (November 2002): 672-676.
PMID
12439043
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Volume
24
Issue
8
Publish Date
2002
Start Page
672
End Page
676

Mxi1, a Myc antagonist, suppresses proliferation of DU145 human prostate cells.

BACKGROUND: Mxi1, an antagonist of c-Myc, maps to human chromosome 10q24-q25, a region altered in a substantial fraction of prostate tumors. Mice deficient for Mxi1 exhibit significant prostate hyperplasia. We studied the ability of Mxi1 to act as a growth suppressor in prostate tumor cells. METHODS: We infected DU145 prostate carcinoma cells with an Mxi1-expressing adenovirus (AdMxi1) in vitro, and measured Mxi1 expression, cell proliferation, soft agar colony formation, and cell cycle distribution. To explore mechanisms of Mxi1-induced growth arrest, we performed gene expression analysis. RESULTS: AdMxi1 infection resulted in reduced cell proliferation, reduced soft agar colony formation, and a higher proportion of cells in the G(2)/M phase of the cell cycle. This G(2)/M growth arrest was associated with elevated levels of cyclin B, and reduced levels of c-MYC and MDM2. CONCLUSIONS: The ability of AdMxi1 to suppress prostate tumor cell proliferation supports a role for Mxi1 loss in the pathogenesis of a subset of human prostate cancers. Prostate 47:194-204, 2001.

Authors
Taj, MM; Tawil, RJ; Engstrom, LD; Zeng, Z; Hwang, C; Sanda, MG; Wechsler, DS
MLA Citation
Taj, MM, Tawil, RJ, Engstrom, LD, Zeng, Z, Hwang, C, Sanda, MG, and Wechsler, DS. "Mxi1, a Myc antagonist, suppresses proliferation of DU145 human prostate cells." Prostate 47.3 (May 15, 2001): 194-204.
PMID
11351349
Source
pubmed
Published In
The Prostate
Volume
47
Issue
3
Publish Date
2001
Start Page
194
End Page
204
DOI
10.1002/pros.1063

Expression of MXI1, a Myc antagonist, is regulated by Sp1 and AP2.

MXI1, a member of the MAD family of Myc antagonists, encodes a transcription factor whose expression must be tightly regulated to maintain normal cell growth and differentiation. To more closely investigate the transcriptional regulation of the human MXI1 gene, we have cloned and characterized the MXI1 promoter. After clarification of the 5'- and 3'-untranslated regions of the cDNA (indicating that the true length of the MXI1 transcript is 2643 base pairs), we identified two transcription initiation sites. We subsequently isolated the MXI1 promoter, which is GC-rich and lacks a TATA box. Although it contains at least six potential initiator sequences, functional studies indicate the proximal two initiator sequences in combination with nearby Sp1 and MED-1 sites together account for virtually all promoter activity. We also demonstrate that MXI1 promoter activity is repressed by high levels of AP2. These studies provide further insight into the complex regulatory mechanisms governing MXI1 gene expression and its role in cellular differentiation and tumor suppression.

Authors
Benson, LQ; Coon, MR; Krueger, LM; Han, GC; Sarnaik, AA; Wechsler, DS
MLA Citation
Benson, LQ, Coon, MR, Krueger, LM, Han, GC, Sarnaik, AA, and Wechsler, DS. "Expression of MXI1, a Myc antagonist, is regulated by Sp1 and AP2." J Biol Chem 274.40 (October 1, 1999): 28794-28802.
PMID
10497252
Source
pubmed
Published In
The Journal of biological chemistry
Volume
274
Issue
40
Publish Date
1999
Start Page
28794
End Page
28802

MXI1, a putative tumor suppressor gene, suppresses growth of human glioblastoma cells.

The Mxi1 protein functions in a regulatory network with members of the c-Myc family, in which c-Myc activates transcription and stimulates cell proliferation, and Mxi1 negatively regulates these actions. Inactivation of the MXI1 gene could, therefore, inhibit differentiation and enhance proliferation in the presence of normal levels of c-Myc, and thus MXI1 is a potential tumor suppressor gene. We and others have previously mapped the MXI1 gene to the distal portion of chromosome 10q, a region that is rearranged or affected by allelic loss in many astrocytic brain tumors. Using a newly described polymorphic CA microsatellite repeat in the third MXI1 intron, we show that 7 of 11 informative glioblastomas demonstrated MXI1 allelic loss. Sequence analysis revealed no somatic mutations in any of the six MXI1 coding exons, similar to findings in prostate tumors with MXI1 allelic loss. To determine whether MXI1 can indeed function as a suppressor of growth, we have introduced a steroid-inducible MXI1 expression vector into the U87MG cell line, a glioblastoma cell line lacking endogenous MXI1 expression. Induction of MXI1 expression resulted in a decreased growth rate and distinct morphological changes. Furthermore, cell cycle analysis demonstrated that induction of MXI1 results in accumulation of cells in the G2-M phase. Thus, these studies support the notion that MXI1 normally functions to suppress cell growth and suggest that loss of MXI1 function may play a role in human glioblastoma development.

Authors
Wechsler, DS; Shelly, CA; Petroff, CA; Dang, CV
MLA Citation
Wechsler, DS, Shelly, CA, Petroff, CA, and Dang, CV. "MXI1, a putative tumor suppressor gene, suppresses growth of human glioblastoma cells." Cancer Res 57.21 (November 1, 1997): 4905-4912.
PMID
9354456
Source
pubmed
Published In
Cancer Research
Volume
57
Issue
21
Publish Date
1997
Start Page
4905
End Page
4912

The MXI1 tumor suppressor gene is regulated by a tata-less promoter

Authors
Quinn, LM; Sarnaik, A; Wechsler, DS
MLA Citation
Quinn, LM, Sarnaik, A, and Wechsler, DS. "The MXI1 tumor suppressor gene is regulated by a tata-less promoter." BLOOD 88.10 (November 15, 1996): 3169-3169.
Source
wos-lite
Published In
Blood
Volume
88
Issue
10
Publish Date
1996
Start Page
3169
End Page
3169

Hemolysis following coil embolization of a patent ductus arteriosus.

We describe the development of hemolysis from moderate residual shunting across a patent ductus arteriosus following coil embolization. The fall in hemoglobin levels from 11.6 to 6.0 gm/dl necessitated a second coil procedure which resulted in complete closure of the residual shunting and resolution of hemolysis. Therefore, appearance of anemia following coil embolization of patent ductus arteriosus should be monitored closely; however, repeat coil embolization with elimination of residual shunt will lead to prompt recovery of normal hemoglobin levels.

Authors
Shim, D; Wechsler, DS; Lloyd, TR; Beekman, RH
MLA Citation
Shim, D, Wechsler, DS, Lloyd, TR, and Beekman, RH. "Hemolysis following coil embolization of a patent ductus arteriosus." Cathet Cardiovasc Diagn 39.3 (November 1996): 287-290.
PMID
8933975
Source
pubmed
Published In
Catheterization and Cardiovascular Diagnosis
Volume
39
Issue
3
Publish Date
1996
Start Page
287
End Page
290
DOI
10.1002/(SICI)1097-0304(199611)39:3<287::AID-CCD17>3.0.CO;2-C

Genomic organization of human MXI1, a putative tumor suppressor gene.

MXI1, a member of the MYC family of transcription factors, is thought to negatively regulate MYC function and may therefore be a potential tumor suppressor gene. Using detailed restriction mapping and partial DNA sequencing analysis, we have determined the genomic organization of the human MXI1 gene to facilitate a search for mutations that affect MXI1 function. The gene spans a region of approximately 60 kb on chromosome 10q24-q25 and comprises six exons. The correspondence of these exons to previously identified Mxi1 functional domains suggests that alternatively spliced transcripts may regulate Mxi1 functional activity. The presence of a cryptic ATG start codon in exon 2 suggests that a functional protein missing the SIN3-interacting domain (exon 1) may be generated by alternative splicing. Finally, we have identified two polymorphic regions within the MXI1 locus: a polymorphic CA repeat in the third intron and an AAAAC polymorphism in the noncoding region of exon 6. These findings will facilitate the analysis of tumors for the presence of inactivating mutations in MXI1 coding and regulatory sequences.

Authors
Wechsler, DS; Shelly, CA; Dang, CV
MLA Citation
Wechsler, DS, Shelly, CA, and Dang, CV. "Genomic organization of human MXI1, a putative tumor suppressor gene." Genomics 32.3 (March 15, 1996): 466-470.
PMID
8838813
Source
pubmed
Published In
Genomics
Volume
32
Issue
3
Publish Date
1996
Start Page
466
End Page
470
DOI
10.1006/geno.1996.0144

TaqI polymorphism of the human MXI1 gene.

Authors
Bova, GS; Wechsler, DS; Van Dang, C; Isaacs, WB
MLA Citation
Bova, GS, Wechsler, DS, Van Dang, C, and Isaacs, WB. "TaqI polymorphism of the human MXI1 gene." Hum Mol Genet 3.12 (December 1994): 2266-.
PMID
7881441
Source
pubmed
Published In
Human Molecular Genetics
Volume
3
Issue
12
Publish Date
1994
Start Page
2266

Localization of the human Mxi1 transcription factor gene (MXI1) to chromosome 10q24-q25.

Authors
Wechsler, DS; Hawkins, AL; Li, X; Jabs, EW; Griffin, CA; Dang, CV
MLA Citation
Wechsler, DS, Hawkins, AL, Li, X, Jabs, EW, Griffin, CA, and Dang, CV. "Localization of the human Mxi1 transcription factor gene (MXI1) to chromosome 10q24-q25." Genomics 21.3 (June 1994): 669-672.
PMID
7959753
Source
pubmed
Published In
Genomics
Volume
21
Issue
3
Publish Date
1994
Start Page
669
End Page
672
DOI
10.1006/geno.1994.1336

Anti-Hu antibody in a neuroblastoma-associated paraneoplastic syndrome.

A 20-month-old infant with Turner syndrome presented with opsoclonus-myoclonus and tonic pupils in association with an abdominal neuroblastoma. Despite complete removal of the tumor, the child developed progressive hearing loss, areflexia, and seizures. Immunohistochemical and Western blot studies of serum and cerebrospinal fluid revealed the presence of anti-Hu antineuronal antibody, which cross-reacted with areas of the patient's tumor. Treatment with intravenous immunoglobulin coincided with the resolution of opsoclonus-myoclonus and the cessation of new neurologic symptoms. This case provides direct support for the autoimmune basis of paraneoplastic symptoms associated with neuroblastoma and suggests that treatment with intravenous immunoglobulin may be of value.

Authors
Fisher, PG; Wechsler, DS; Singer, HS
MLA Citation
Fisher, PG, Wechsler, DS, and Singer, HS. "Anti-Hu antibody in a neuroblastoma-associated paraneoplastic syndrome." Pediatr Neurol 10.4 (June 1994): 309-312.
PMID
8068157
Source
pubmed
Published In
Pediatric Neurology
Volume
10
Issue
4
Publish Date
1994
Start Page
309
End Page
312

Differential binding of c-Myc and Max to nucleosomal DNA.

The ability of a transcription factor to function in vivo must be determined in part by its ability to bind to its recognition site in chromatin. We have used Max and derivatives of c-Myc to characterize the effect of changes of dimerization partner on binding to nucleosomal DNA templates. We find that homo- and heterodimeric complexes of these proteins bind to the CACGTG sequence in free DNA with similar affinities. Although Max homodimers bind to nucleosomes, truncated c-Myc homodimers do not. Surprisingly, modifying the c-Myc dimerization interface or changing its dimerization partner to Max enables nucleosomal DNA binding. Thus, changes in dimer structure or dimerization efficiency can have significant effects on nucleosome binding that are not predicted from their affinity for free DNA. We conclude that domains other than the basic region per se influence the ability of a transcription factor to bind to nucleosomal DNA and that changes of dimerization partner can directly affect the ability of a factor to occupy nucleosomal binding sites.

Authors
Wechsler, DS; Papoulas, O; Dang, CV; Kingston, RE
MLA Citation
Wechsler, DS, Papoulas, O, Dang, CV, and Kingston, RE. "Differential binding of c-Myc and Max to nucleosomal DNA." Mol Cell Biol 14.6 (June 1994): 4097-4107.
PMID
8196648
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
14
Issue
6
Publish Date
1994
Start Page
4097
End Page
4107

Yersinia enterocolitica infection in a patient with sickle cell disease after exposure to chitterlings.

PURPOSE: We describe certain clinical, epidemiologic, and host-susceptibility features of Yersinia enterocolitica infection in the context of a patient with underlying risk factors. PATIENTS AND METHODS: A 10-year-old black girl with sickle cell disease receiving chelation therapy for iron overload resulting from chronic transfusion therapy was admitted with acute abdominal pain and fever. RESULTS: Upon hospital admission, differential diagnoses included enterocolitis, appendicitis, and vasoocclusive crisis. On the 6th hospital day, the patient's stool culture became positive for Y. enterocolitica. Household exposure to raw pork intestines (chitterlings) was the presumed source of the infection. Deferoxamine therapy was withheld, and antibiotic therapy was administered with subsequent clinical improvement. CONCLUSIONS: Y. enterocolitica infection should be considered as a cause of abdominal pain mimicking appendicitis in patients with underlying risk factors (including certain sickle cell patients). History of exposure to raw or undercooked pork products and appropriate cultures should be obtained. Deferoxamine therapy should be withheld in iron-overloaded patients presenting with such symptoms because deferoxamine and iron overload constitute independent risk factors for Yersinia infection. Such patients should be advised to avoid potential exposures to this pathogen.

Authors
Stoddard, JJ; Wechsler, DS; Nataro, JP; Casella, JF
MLA Citation
Stoddard, JJ, Wechsler, DS, Nataro, JP, and Casella, JF. "Yersinia enterocolitica infection in a patient with sickle cell disease after exposure to chitterlings." Am J Pediatr Hematol Oncol 16.2 (May 1994): 153-155.
PMID
8166368
Source
pubmed
Published In
American Journal of Pediatric Hematology/Oncology
Volume
16
Issue
2
Publish Date
1994
Start Page
153
End Page
155

Cytogenetic abnormalities in two cases of neuroblastoma.

Neuroblastomas are common solid tumors in children. We report chromosome analysis of two neuroblastomas, each studied at diagnosis and at recurrence. The first case was a clinical stage D tumor which showed 45,X-Y, add(1)(p34),der(15)t(Y;15)(q11;p13), and double minutes on cytogenetic analysis at diagnosis. At recurrence, the same structural abnormalities were present along with a homogeneously staining region (hsr) at 8q22, 19p12, or 3p23 in each of three related clones. The hsr were shown to represent amplification of the N-myc gene by in situ hybridization. Cytogenetic analysis of the second tumor, stage D-S, showed 48-54,XX,der(1)add (1)(q41), +2, +7, +7, inv(9), +17, + mar. The lack of demonstrative involvement of 1p or visible evidence of gene amplification has also characterized the limited number of D-S specimens previously described, suggesting that stage D-S neuroblastoma indeed differs from stage D disease at the genetic level.

Authors
Lo, R; Perlman, E; Hawkins, AL; Hayashi, R; Wechsler, DS; Look, AT; Griffin, CA
MLA Citation
Lo, R, Perlman, E, Hawkins, AL, Hayashi, R, Wechsler, DS, Look, AT, and Griffin, CA. "Cytogenetic abnormalities in two cases of neuroblastoma." Cancer Genet Cytogenet 74.1 (May 1994): 30-34.
PMID
8194044
Source
pubmed
Published In
Cancer Genetics and Cytogenetics
Volume
74
Issue
1
Publish Date
1994
Start Page
30
End Page
34

Resolution of nephrocalcinosis associated with tumor lysis syndrome.

Authors
Wechsler, DS; Kastan, MB; Fivush, BA
MLA Citation
Wechsler, DS, Kastan, MB, and Fivush, BA. "Resolution of nephrocalcinosis associated with tumor lysis syndrome." Pediatr Hematol Oncol 11.1 (January 1994): 115-118. (Letter)
PMID
8155494
Source
pubmed
Published In
Pediatric Hematology-Oncology (Informa)
Volume
11
Issue
1
Publish Date
1994
Start Page
115
End Page
118

Dermatitis as a Presenting Sign of Cystic Fibrosis

Authors
Darmstadt, GL
MLA Citation
Darmstadt, GL. "Dermatitis as a Presenting Sign of Cystic Fibrosis." Archives of Dermatology 128.10 (October 1, 1992): 1358-1358.
Source
crossref
Published In
Archives of Dermatology
Volume
128
Issue
10
Publish Date
1992
Start Page
1358
End Page
1358
DOI
10.1001/archderm.1992.01680200068009

Dermatitis as a presenting sign of cystic fibrosis.

BACKGROUND: Three percent to 13% of patients with cystic fibrosis present with protein-energy malnutrition that is characterized by hypoproteinemia, edema, and anemia and is associated with high morbidity and mortality. Cutaneous manifestations of malnutrition are rare in patients with cystic fibrosis and have been attributed to deficiencies of protein, zinc, and essential fatty acids. OBSERVATIONS: We describe five patients who presented with failure to thrive, hypoproteinemia, edema, and a cutaneous eruption before the onset of pulmonary symptoms and before the diagnosis of cystic fibrosis was made. The rash had a predilection for the extremities (lower > upper), perineum, and periorificial surfaces. In most cases, erythematous, scaling papules developed by 4 months of age and progressed within 1 to 3 months to extensive, desquamating plaques. Alopecia was variable, and mucous membrane or nail involvement was not observed. The rash was associated with malnutrition and resolved in all survivors within 10 days of providing pancreatic enzyme and nutritional supplementation. The pathogenesis of the rash is unclear, but it appears to stem from deficiencies of zinc, protein, and essential fatty acids and may be mediated by alterations in prostaglandin metabolism. CONCLUSIONS: Cystic fibrosis should be included in the differential diagnosis of the red, scaly infant, particularly when failure to thrive, hypoproteinemia, and edema are also present. Recognition of rash as a sign of cystic fibrosis complicated by protein-energy malnutrition will allow earlier diagnosis and treatment of these patients and may improve their outcome.

Authors
Darmstadt, GL; Schmidt, CP; Wechsler, DS; Tunnessen, WW; Rosenstein, BJ
MLA Citation
Darmstadt, GL, Schmidt, CP, Wechsler, DS, Tunnessen, WW, and Rosenstein, BJ. "Dermatitis as a presenting sign of cystic fibrosis." Arch Dermatol 128.10 (October 1992): 1358-1364. (Review)
PMID
1417024
Source
pubmed
Published In
Archives of Dermatology
Volume
128
Issue
10
Publish Date
1992
Start Page
1358
End Page
1364

Opposite orientations of DNA bending by c-Myc and Max.

The control of gene transcription requires specific protein-protein and protein-DNA interactions. c-Myc, the protein product of the c-myc protooncogene, is a member of the basic helix-loop-helix leucine-zipper class of transcription factors. Although c-Myc is able to bind to a specific core hexanucleotide DNA sequence (CACGTG), its precise function in modulating transcription remains unclear. The recent discovery of Max, a basic helix-loop-helix leucine-zipper partner protein for c-Myc, suggests that the ability of c-Myc to regulate transcription is modulated by the presence of Max. By taking advantage of the altered mobility of protein-bound DNA in the mobility-shift assay, we demonstrate the homo- and heterodimeric complexes of c-Myc and Max are able to cause increased DNA flexure as measured by the circular permutation assay. Based on phasing analysis, c-Myc and Max homodimers bend DNA in opposite orientations, whereas c-Myc-Max heterodimers cause a smaller bend, in an orientation similar to that induced by Max homodimers. To address the possibility that the apparent opposite orientation of bending was the result of DNA unwinding by one of the proteins, we measured the ability of c-Myc and Max homodimers to affect DNA unwinding; we were unable to show any specific unwinding caused by c-Myc or Max. In addition to demonstrating that members of the basic helix-loop-helix leucine-zipper class of transcription factors are able to induce DNA bending, these results suggest that different transcription factor dimers are able to bind to identical DNA sequences and yet have distinct structural effects.

Authors
Wechsler, DS; Dang, CV
MLA Citation
Wechsler, DS, and Dang, CV. "Opposite orientations of DNA bending by c-Myc and Max." Proc Natl Acad Sci U S A 89.16 (August 15, 1992): 7635-7639.
PMID
1323849
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
89
Issue
16
Publish Date
1992
Start Page
7635
End Page
7639

DNA binding by the Myc oncoproteins.

The c-Myc protein is a potential activator of transcription, with the ability to bind in a heterodimer form with Max to DNA sequences containing the core hexanucleotide sequence CAC(G/A)TG. These properties are shared with L-Myc, a homologous oncoprotein expressed in small cell lung carcinoma cells; with N-Myc, expressed in neuroblastoma cells; and with avian v-Myc, the c-Myc homolog expressed by a chicken retrovirus. The c-Myc, and probably v-Myc, proteins also have nonspecific DNA binding function, which may improve the kinetics of specific DNA binding. Curiously, this domain appears not to be conserved in L-Myc or N-Myc [22]. The data that have accumulated to date are consistent with a model in which a c-Myc/Max heterodimer positively regulates the transcription of growth-related genes, with Max homodimer functioning as a negative regulator of the same genes (Fig. 4) [55]. Max is expressed constitutively at low levels, whereas c-Myc is expressed at low levels in quiescent cells, but high levels of c-Myc are induced by mitogenic stimulation [56]. Thus, in proliferating cells c-Myc/Max heterodimers might bind to the regulatory elements of growth-related genes, where the c-Myc TAD might stimulate transcription. Conversely, in quiescent cells with little c-Myc present, Max homodimers might predominate. They might bind to exactly the same regulatory elements, but due to the apparent absence of a TAD in Max [36], transcription might be repressed. Validation of this model will require the demonstration of clear regulation of a physiological promoter of a growth-related gene by c-Myc/Max. Although it is widely believed that Myc proteins function as transcriptional activators, this hypothesis has only been conclusively supported recently [57, 58]. A theory that c-Myc plays a role in DNA replication is not as well substantiated at this point. It is even possible that Myc might be involved in both transcription and replication. Although the function of these fascinating proteins has been enigmatic for a decade, the rate of progress in our understanding of Myc function is accelerating. Such progress will undoubtedly lead to a deeper appreciation of this protein, which lies at the crossroads of cellular proliferation and oncogenesis.

Authors
Kato, GJ; Wechsler, DS; Dang, CV
MLA Citation
Kato, GJ, Wechsler, DS, and Dang, CV. "DNA binding by the Myc oncoproteins." Cancer Treat Res 63 (1992): 313-325. (Review)
PMID
1363364
Source
pubmed
Published In
Cancer Treatment and Research
Volume
63
Publish Date
1992
Start Page
313
End Page
325

Apparent proteinuria as a consequnce of sodium bicarbonate ingestion

Authors
Wechsler, D; Ibsen, L; Fosarelli, P
MLA Citation
Wechsler, D, Ibsen, L, and Fosarelli, P. "Apparent proteinuria as a consequnce of sodium bicarbonate ingestion." Pediatrics 86.2 (1990): 318-319.
PMID
2164657
Source
scival
Published In
Pediatrics
Volume
86
Issue
2
Publish Date
1990
Start Page
318
End Page
319

Further characterization of the curative antibodies in Trypanosoma musculi infection.

The ability of immune plasma (IP) taken from different donor strains of mice to cure Trypanosoma musculi infection in various recipient mouse strains, when given during the plateau phase of infection, was examined. C57BL/6, B10.A/SgSn, B10.D2/oSn, B10.D2/nSn, DBA/2, and BALB/c strains could be cured of parasitemia (giving 0.4 to 0.8 ml of IP per mouse), whereas A/J and C3H/HeN strains could not (giving up to 1.2 ml of IP per mouse). Noncure appeared to be associated with the high-plateau parasitemias (approximately 10(8] that developed in the latter strains since IP administered early in infection, when the parasite burden was similar to the plateau parasitemias (approximately 10(6] of strains that could be cured, was at least partially effective in A/J and C3H/HeN mice. The IP of any strain tested (C57BL/6, B10.D2/oSn, B10.D2/nSn, DBA/2, A/J, or C3H/HeN) could bring about elimination of trypanosomes in strains able to be cured. The potency of IP from different strains varied, being greater in the strains that developed higher-plateau parasitemias. Potency of IP appears to correlate positively with the titers of trypanosome-specific antibody of the immunoglobulin G2a isotype (the curative antibody). The role of the late-acting complement components was examined. In C5-deficient mice the course of infection was normal, although the elimination phase was delayed by a few days. Cure of parasitemia by IP administered during the plateau phase was equally effective in the presence or absence of C5 in either the donor or the recipient. When tested in vitro, however, IP only exhibited antitrypanosomal activity when added to infected blood taken from C5-sufficient strains of mice. We conclude that in vitro, under the conditions used in the assay, antibody-mediated destruction of the trypanosomes is brought about by complement-mediated lysis. This process, although it probably occurs to some extent, is unlikely to be the major mechanism of trypanosome elimination in vivo.

Authors
Wechsler, DS; Kongshavn, PA
MLA Citation
Wechsler, DS, and Kongshavn, PA. "Further characterization of the curative antibodies in Trypanosoma musculi infection." Infect Immun 56.9 (September 1988): 2379-2384.
PMID
3410542
Source
pubmed
Published In
Infection and immunity
Volume
56
Issue
9
Publish Date
1988
Start Page
2379
End Page
2384

Heat-labile IgG2a antibodies affect cure of Trypanosoma musculi infection in C57BL/6 mice.

Immune plasma (IP) obtained from mice cured of Trypanosoma musculi infection is able to mediate trypanosome clearance both in vivo and in vitro. A protein A-derived immunoglobulin fraction of IP containing primarily IgG2a and IgG3 shares this curative activity. Additional purification of IP with the use of anti-IgG2a and anti-IgG3 coupled to Sepharose beads demonstrates that the curative activity of IP resides solely in the IgG2a fraction; IP depleted of IgG2a is no longer able to effect T. musculi removal. Furthermore, this curative IgG2a is labile to heat treatment for 30 min at 56 degrees C. Enzyme-linked immunosorbent assays show that trypanosome-specific IgG2a builds up gradually over the course of infection, and temporarily drops slightly at the time of parasite clearance.

Authors
Wechsler, DS; Kongshavn, PA
MLA Citation
Wechsler, DS, and Kongshavn, PA. "Heat-labile IgG2a antibodies affect cure of Trypanosoma musculi infection in C57BL/6 mice." J Immunol 137.9 (November 1, 1986): 2968-2972.
PMID
3760578
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
137
Issue
9
Publish Date
1986
Start Page
2968
End Page
2972

INVITRO ASSAY FOR CURATIVE ACTIVITY IN BLOOD OF MICE INFECTED WITH TRYPANOSOMA-MUSCULI

Authors
WECHSLER, DS; KONGSHAVN, PAL
MLA Citation
WECHSLER, DS, and KONGSHAVN, PAL. "INVITRO ASSAY FOR CURATIVE ACTIVITY IN BLOOD OF MICE INFECTED WITH TRYPANOSOMA-MUSCULI." INFECTION AND IMMUNITY 53.2 (August 1986): 240-244.
Source
wos-lite
Published In
Infection and immunity
Volume
53
Issue
2
Publish Date
1986
Start Page
240
End Page
244

In vitro assay for curative activity in blood of mice infected with Trypanosoma musculi.

An in vitro assay for curative antibody present in plasma of mice cured of Trypanosoma musculi is described. The assay involves the addition of plasma to a sample of infected blood, followed by hourly monitoring of the parasite count therein. Immune plasma effected a significant reduction in parasite number, whereas normal mouse plasma did not. Heat treatment of immune plasma for 30 min at 56 degrees C abolished its ability to effect any reduction. The assay is simple, rapid, and economical and correlates well with results of all in vivo studies performed to date.

Authors
Wechsler, DS; Kongshavn, PA
MLA Citation
Wechsler, DS, and Kongshavn, PA. "In vitro assay for curative activity in blood of mice infected with Trypanosoma musculi." Infect Immun 53.2 (August 1986): 240-244.
PMID
3733217
Source
pubmed
Published In
Infection and immunity
Volume
53
Issue
2
Publish Date
1986
Start Page
240
End Page
244

Characterization of antibodies mediating protection and cure of Trypanosoma musculi infection in mice.

Plasma samples were collected from mice infected with Trypanosoma musculi at different times postinfection and administered to naive recipient mice either before or during T. musculi infection. The protective and curative activities of these plasma samples were shown to increase as the time of collection postinfection increased; plasma collected at 14 days postinfection was partially protective and partially curative, whereas that collected at 28 days postinfection was completely protective and curative. The curative activity was labile to heat treatment (30 min at 56 degrees C), whereas the protective activity was heat stable. Additional kinetic parameters relating to the efficacy of protection were investigated. Evidence is presented that both activities are immunoglobulin in nature. Protein A-Sepharose chromatography indicated that the activities are associated with the immunoglobulin G2a or immunoglobulin G3 subclasses of immunoglobulin G. The curative antibody appears to be intrinsically heat labile, since heat treatment of a purified immunoglobulin preparation abolished the ability to cure. Studies on the mechanism of parasite elimination from blood suggest that the process not only requires antibody but is also complement dependent.

Authors
Wechsler, DS; Kongshavn, PA
MLA Citation
Wechsler, DS, and Kongshavn, PA. "Characterization of antibodies mediating protection and cure of Trypanosoma musculi infection in mice." Infect Immun 48.3 (June 1985): 787-794.
PMID
3997247
Source
pubmed
Published In
Infection and immunity
Volume
48
Issue
3
Publish Date
1985
Start Page
787
End Page
794

Combinational diversity within variable regions bearing the predominant anti-p-azophenylarsonate idiotype of strain A mice.

The humoral immune response in strain A mice to protein conjugates of p-azophenylarsonate (Ars) is characterized by the presence of a major cross-reactive idiotype denoted as IdCR. Previous molecular analyses of monoclonal IdCR+ Ars-binding antibodies isolated from multiply immunized animals have indicated that these antibody variable (V) regions may be the expressed product of a single combination of VH, D, JH, V kappa, and J kappa gene segments. The basis of this apparent domination of the Ars response by V regions encoded by this single combination of gene segments is unclear, but is discussed in this report. Our structural analyses on five monoclonal IdCR+ antibodies that are unable to bind Ars show that in contrast to those of Ars-binding IdCR+ antibodies, these (Ars-nonbinding) IdCR+ V regions are encoded by multiple combinations of VH, D, JH, V kappa, and J kappa gene segments, but with the commonality that they all utilize a single VH gene segment (VHIdCR). We provide examples in which the VHIdCR gene segment is expressed with three different V kappa gene segments and with each of the four JH gene segments to produce serologically detectable IdCR+ Ars-nonbinding antibodies. It would thus appear that the previous failure to detect alternative IdCR+ V segment combinations was due to a sampling procedure requiring that the IdCR+ antibody bind Ars, and not the result of restricted assembly or expression of the VHIdCR gene segment with a particular combination of D, JH, V kappa, and J kappa gene segments. This bias in protocol, however, cannot completely account for the homogeneity in previously studied IdCR+ Ars-binding antibodies, because we were able to isolate, from primary immune responses, IdCR+ antibodies that do bind Ars but that utilize alternative V segment combinations. This finding suggests that combinations of V gene segments encoding IdCR+ antibodies are more numerous in primary as opposed to secondary immune responses, and raises the question of why a single combination of VH, D, JH, V kappa, and J kappa gene segments dominates the secondary strain A immune response to Ars.

Authors
Wysocki, LJ; Margolies, MN; Huang, B; Nemazee, DA; Wechsler, DS; Sato, VL; Smith, JA; Gefter, ML
MLA Citation
Wysocki, LJ, Margolies, MN, Huang, B, Nemazee, DA, Wechsler, DS, Sato, VL, Smith, JA, and Gefter, ML. "Combinational diversity within variable regions bearing the predominant anti-p-azophenylarsonate idiotype of strain A mice." J Immunol 134.4 (April 1985): 2740-2747.
PMID
2982953
Source
pubmed
Published In
Journal of immunology (Baltimore, Md. : 1950)
Volume
134
Issue
4
Publish Date
1985
Start Page
2740
End Page
2747

Cure of Trypanosoma musculi infection by heat-labile activity in immune plasma.

Passive transfer of plasma from a mouse cured of parasitemia to a Trypanosoma musculi-infected host rapidly eliminates parasitemia; this curative activity, presumably mediated by an immunoglobulin, is sensitive to heat treatment (56 degrees C, 30 min). In addition, pretreatment with immune plasma, even after heat treatment, prevents the development of a patent parasitemia in a naive host (protective activity).

Authors
Wechsler, DS; Kongshavn, PA
MLA Citation
Wechsler, DS, and Kongshavn, PA. "Cure of Trypanosoma musculi infection by heat-labile activity in immune plasma." Infect Immun 44.3 (June 1984): 756-759.
PMID
6724698
Source
pubmed
Published In
Infection and immunity
Volume
44
Issue
3
Publish Date
1984
Start Page
756
End Page
759

CHARACTERIZATION OF THERMOLABILE CURATIVE ACTIVITY IN PLASMA OF MICE INFECTED WITH TRYPANOSOMA MUSCULI

Authors
WECHSLER, DS; KONGSHAVN, PAL
MLA Citation
WECHSLER, DS, and KONGSHAVN, PAL. "CHARACTERIZATION OF THERMOLABILE CURATIVE ACTIVITY IN PLASMA OF MICE INFECTED WITH TRYPANOSOMA MUSCULI." JOURNAL OF LEUKOCYTE BIOLOGY 36.3 (1984): 399-399.
Source
wos-lite
Published In
Journal of leukocyte biology
Volume
36
Issue
3
Publish Date
1984
Start Page
399
End Page
399

Thermolabile curative and thermostable protective activities in plasma of mice infected with Trypanosoma musculi

Authors
Wechsler, DS; Korgsham, PAL
MLA Citation
Wechsler, DS, and Korgsham, PAL. "Thermolabile curative and thermostable protective activities in plasma of mice infected with Trypanosoma musculi." Federation Proceedings 43.6 (1984): no.-2060.
Source
scival
Published In
Federation Proceedings
Volume
43
Issue
6
Publish Date
1984
Start Page
no.
End Page
2060

MECHANISMS OF PROTECTIVE IMMUNITY IN MURINE TRYPANOSOMIASIS - ELIMINATION OF BLOOD PARASITEMIA INVOLVES CELLULAR MECHANISM

Authors
KONGSHAVN, PAL; STCHARLES, C; WECHSLER, D; RAPPATONI, W; GHADIRIAN, E
MLA Citation
KONGSHAVN, PAL, STCHARLES, C, WECHSLER, D, RAPPATONI, W, and GHADIRIAN, E. "MECHANISMS OF PROTECTIVE IMMUNITY IN MURINE TRYPANOSOMIASIS - ELIMINATION OF BLOOD PARASITEMIA INVOLVES CELLULAR MECHANISM." FEDERATION PROCEEDINGS 41.3 (1982): 581-581.
Source
wos-lite
Published In
The FASEB Journal
Volume
41
Issue
3
Publish Date
1982
Start Page
581
End Page
581
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