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Rein, Lindsay Anne Magura

Positions:

Assistant Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2008

M.D. — University of North Dakota School of Medicine and Health Sciences

Resident, Internal Medicine

Duke University School of Medicine

Grants:

Targeting Beta-arrestins in myeloid malignancies

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
American Society of Hematology
Role
Principal Investigator
Start Date
July 01, 2018
End Date
June 30, 2019

B-arrestin2 and the disease course of chronic myeloid leukemia (CML)

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
American Society of Hematology
Role
PI-Fellow
Start Date
July 01, 2014
End Date
June 30, 2015

Publications:

Applications of Gene Editing Technologies to Cellular Therapies.

Hematologic malignancies are characterized by genetic heterogeneity, making classic gene therapy with a goal of correcting 1 genetic defect ineffective in many of these diseases. Despite initial tribulations, gene therapy, as a field, has grown by leaps and bounds with the recent development of gene editing techniques including zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR) sequences and CRISPR-associated protein-9 (Cas9) nuclease or CRISPR/Cas9. These novel technologies have been applied to efficiently and specifically modify genetic information in target and effector cells. In particular, CRISPR/Cas9 technology has been applied to various hematologic malignancies and has also been used to modify and improve chimeric antigen receptor-modified T cells for the purpose of providing effective cellular therapies. Although gene editing is in its infancy in malignant hematologic diseases, there is much room for growth and application in the future.

Authors
Rein, LAM; Yang, H; Chao, NJ
MLA Citation
Rein, LAM, Yang, H, and Chao, NJ. "Applications of Gene Editing Technologies to Cellular Therapies." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation 24.8 (August 2018): 1537-1545. (Review)
PMID
29601858
Source
epmc
Published In
Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Volume
24
Issue
8
Publish Date
2018
Start Page
1537
End Page
1545
DOI
10.1016/j.bbmt.2018.03.021

β-Arrestin2 mediates progression of murine primary myelofibrosis.

Primary myelofibrosis is a myeloproliferative neoplasm associated with significant morbidity and mortality, for which effective therapies are lacking. β-Arrestins are multifunctional adaptor proteins involved in developmental signaling pathways. One isoform, β-arrestin2 (βarr2), has been implicated in initiation and progression of chronic myeloid leukemia, another myeloproliferative neoplasm closely related to primary myelofibrosis. Accordingly, we investigated the relationship between βarr2 and primary myelofibrosis. In a murine model of MPLW515L-mutant primary myelofibrosis, mice transplanted with donor βarr2-knockout (βarr2-/-) hematopoietic stem cells infected with MPL-mutant retrovirus did not develop myelofibrosis, whereas controls uniformly succumbed to disease. Although transplanted βarr2-/- cells homed properly to marrow, they did not repopulate long-term due to increased apoptosis and decreased self-renewal of βarr2-/- cells. In order to assess the effect of acute loss of βarr2 in established primary myelofibrosis in vivo, we utilized a tamoxifen-induced Cre-conditional βarr2-knockout mouse. Mice that received Cre (+) donor cells and developed myelofibrosis had significantly improved survival compared with controls. These data indicate that lack of antiapoptotic βarr2 mediates marrow failure of murine hematopoietic stem cells overexpressing MPLW515L. They also indicate that βarr2 is necessary for progression of primary myelofibrosis, suggesting that it may serve as a novel therapeutic target in this disease.

Authors
Rein, LA; Wisler, JW; Kim, J; Theriot, B; Huang, L; Price, T; Yang, H; Chen, M; Chen, W; Sipkins, D; Fedoriw, Y; Walker, JK; Premont, RT; Lefkowitz, RJ
MLA Citation
Rein, LA, Wisler, JW, Kim, J, Theriot, B, Huang, L, Price, T, Yang, H, Chen, M, Chen, W, Sipkins, D, Fedoriw, Y, Walker, JK, Premont, RT, and Lefkowitz, RJ. "β-Arrestin2 mediates progression of murine primary myelofibrosis." JCI insight 2.24 (December 21, 2017).
PMID
29263312
Source
epmc
Published In
Jci Insight
Volume
2
Issue
24
Publish Date
2017
DOI
10.1172/jci.insight.98094

NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018.

Myeloproliferative neoplasms (MPNs) are a group of heterogeneous disorders of the hematopoietic system that include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). PV and ET are characterized by significant thrombohemorrhagic complications and a high risk of transformation to MF and acute myeloid leukemia. The diagnosis and management of PV and ET has evolved since the identification of mutations implicated in their pathogenesis. These NCCN Guideline Insights discuss the recommendations outlined in the NCCN Guidelines for the risk stratification, treatment, and special considerations for the management of PV and ET.

Authors
Mesa, RA; Jamieson, C; Bhatia, R; Deininger, MW; Fletcher, CD; Gerds, AT; Gojo, I; Gotlib, J; Gundabolu, K; Hobbs, G; McMahon, B; Mohan, SR; Oh, S; Padron, E; Papadantonakis, N; Pancari, P; Podoltsev, N; Rampal, R; Ranheim, E; Reddy, V; Rein, LAM; Scott, B; Snyder, DS; Stein, BL; Talpaz, M; Verstovsek, S; Wadleigh, M; Wang, ES; Bergman, MA; Gregory, KM; Sundar, H
MLA Citation
Mesa, RA, Jamieson, C, Bhatia, R, Deininger, MW, Fletcher, CD, Gerds, AT, Gojo, I, Gotlib, J, Gundabolu, K, Hobbs, G, McMahon, B, Mohan, SR, Oh, S, Padron, E, Papadantonakis, N, Pancari, P, Podoltsev, N, Rampal, R, Ranheim, E, Reddy, V, Rein, LAM, Scott, B, Snyder, DS, Stein, BL, Talpaz, M, Verstovsek, S, Wadleigh, M, Wang, ES, Bergman, MA, Gregory, KM, and Sundar, H. "NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018." Journal of the National Comprehensive Cancer Network : Jnccn 15.10 (October 2017): 1193-1207.
PMID
28982745
Source
epmc
Published In
Jnccn Journal of the National Comprehensive Cancer Network
Volume
15
Issue
10
Publish Date
2017
Start Page
1193
End Page
1207
DOI
10.6004/jnccn.2017.0157

Clinical potential of elacytarabine in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) has been treated for over four decades with standard induction chemotherapy including seven days of cytosine arabinoside (cytarabine, ara-C) infusion. Cytarabine, while effective in killing leukemic cells, is subject to development of several resistance mechanisms rendering the drug ineffective in many patients. Elacytarabine, a lipophilic 5'-elaidic acid ester or nucleoside analogue of cytosine arabinoside, was created with the intent of overcoming resistance mechanisms including reduced expression of the human equilibrative nucleoside transporter 1 (hENT1) required for cytarabine entry into cells, as well as increased activity of cytidine deaminase (CDA) which breaks down the active metabolite of cytarabine, ara-CTP. Elacytarabine enters cells independently of transporters, has a longer half life compared with cytarabine and is not subject to deactivation by CDA. Preclinical data were encouraging although subsequent clinical studies have failed to show superiority of elacytarabine compared with standard of care as monotherapy in patients with AML. Clinical trials utilizing elacytarabine in combination with anthracyclines are ongoing. Use of hENT1 expression as a predictive marker for cytarabine or elacytarabine response has been studied with no conclusive validation to date. Despite promising early results, the jury is still out in regards to this novel agent as an effective alternative to standard cytarabine therapy in acute leukemias, especially in combination with additional agents such as anthracyclines.

Authors
Rein, LAM; Rizzieri, DA
MLA Citation
Rein, LAM, and Rizzieri, DA. "Clinical potential of elacytarabine in patients with acute myeloid leukemia." Therapeutic advances in hematology 5.6 (December 2014): 211-220. (Review)
PMID
25469211
Source
epmc
Published In
Therapeutic Advances in Hematology
Volume
5
Issue
6
Publish Date
2014
Start Page
211
End Page
220
DOI
10.1177/2040620714552615

WT1 vaccination in acute myeloid leukemia: new methods of implementing adoptive immunotherapy.

INTRODUCTION: The Wilms tumor 1 (WT1) gene was originally identified as a tumor suppressor gene that, when mutated, would lead to the development of pediatric renal tumors. More recently, it has been determined that WT1 is overexpressed in 90% of patients with acute myeloid leukemia (AML) and is mutated in approximately 10% of AML patients. WT1 plays a role in normal hematopoiesis and, in AML specifically, it has oncogenic function and plays an important role in cellular proliferation and differentiation. The ubiquity of WT1 in leukemia has lead to the development of vaccines aimed at employing the host immune system to mount a T-cell response to a known antigen. AREAS COVERED: In this evaluation, the authors discuss the role of WT1 in normal hematopoiesis as well as in the development of hematologic malignancies. Furthermore, the authors discuss the data supporting the development of WT1 vaccines, and the clinical trials supporting their use in patients with acute leukemia. EXPERT OPINION: Several small trials have been conducted which support the safety and efficacy of this therapy, although larger trials are certainly warranted. In the authors' opinion, the WT1 vaccination has potential in terms of its application as an adjuvant therapy for patients with AML who are at high risk of relapse or who have detectable minimal residual disease after initial standard therapy.

Authors
Rein, LAM; Chao, NJ
MLA Citation
Rein, LAM, and Chao, NJ. "WT1 vaccination in acute myeloid leukemia: new methods of implementing adoptive immunotherapy." Expert opinion on investigational drugs 23.3 (March 2014): 417-426. (Review)
PMID
24521058
Source
epmc
Published In
Expert Opinion on Investigational Drugs
Volume
23
Issue
3
Publish Date
2014
Start Page
417
End Page
426
DOI
10.1517/13543784.2014.889114

Statin use and need for therapy in chronic lymphocytic leukemia

Authors
Friedman, DR; Magura, LA; Warren, HAC; Harrison, JD; Diehl, LF; Weinberg, JB
MLA Citation
Friedman, DR, Magura, LA, Warren, HAC, Harrison, JD, Diehl, LF, and Weinberg, JB. "Statin use and need for therapy in chronic lymphocytic leukemia." Leukemia and Lymphoma 51.12 (2010): 2295-2298.
PMID
20929315
Source
scival
Published In
Leukemia & Lymphoma
Volume
51
Issue
12
Publish Date
2010
Start Page
2295
End Page
2298
DOI
10.3109/10428194.2010.520050

Hypercholesterolemia and prostate cancer: a hospital-based case-control study.

OBJECTIVE: High levels of serum cholesterol have been proposed to increase the risk of prostate cancer but the epidemiologic evidence is limited. METHODS: We conducted a hospital-based case-control study in Fargo, ND, USA, to examine the association between hypercholesterolemia and prostate cancer. Cases were men with incident, histologically confirmed prostate cancer. Controls were men without clinical cancer who were seen at the same hospital for an annual physical exam. Demographic and clinical data were abstracted from patients' medical charts. RESULTS: From a patient population aged 50 to 74 years old, we obtained data on 312 White cases and 319 White controls. Hypercholesterolemia was defined as total cholesterol greater than 5.17 (mmol/l). Univariate logistic regression showed a significant association between hypercholesterolemia and prostate cancer (odds ratio (OR) = 1.64, 95% confidence interval (CI): 1.19-2.27). This association changed only slightly after adjustment for age, family history of prostate cancer, body mass index, type 2 diabetes, smoking, and multivitamin use (OR = 1.58, 95% CI: 1.11-2.24). A significant association was found between low HDL and prostate cancer (OR = 1.57, 95% CI: 1.04-2.36). High LDL was associated with a 60% increased risk for prostate cancer (OR = 1.60, 95% CI: 1.09-2.34). Compared to never smokers, current smokers had an 84% increased risk for prostate cancer (OR = 1.84, 95% CI: 1.09-3.13). CONCLUSION: This study adds to recent evidence that hypercholesterolemia may increase the risk of prostate cancer in white men.

Authors
Magura, L; Blanchard, R; Hope, B; Beal, JR; Schwartz, GG; Sahmoun, AE
MLA Citation
Magura, L, Blanchard, R, Hope, B, Beal, JR, Schwartz, GG, and Sahmoun, AE. "Hypercholesterolemia and prostate cancer: a hospital-based case-control study." Cancer causes & control : CCC 19.10 (December 2008): 1259-1266.
PMID
18704722
Source
epmc
Published In
Cancer Causes & Control : Ccc
Volume
19
Issue
10
Publish Date
2008
Start Page
1259
End Page
1266
DOI
10.1007/s10552-008-9197-7
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