Ken Young

Overview:

I am a clinically-oriented diagnostic physician with clinical expertise in the pathologic diagnosis of hematologic cancers including tumors of the bone marrow, lymphoid tissue, spleen and pre-malignant hematologic conditions. Another area of interest is blood cancer classification with molecular and genetic profiling. In my research program, we focus on molecular mechanisms of tumor progression, cell-of-origin, biomarkers, and novel therapeutic strategies in lymphoma, myeloma and leukemia. In addition to patient care and translational research, medical education and scientific communication are also part of interest. I provide persistent support for the physician-scientist program and Blood Cancer Pathology program in the department and cancer center. Many residents, fellows, graduates and postdocs have worked and been trained in our program. We perform comprehensive clinical and research functions that include bone marrow, lymphoma pathology, clinical flow cytometry, cytogenetics, molecular diagnostics and outside services.

I am currently the director of hematopathology division that provides diagnostic consultation services and relevant specialized testing for patients with various types of acute and chronic leukemia, lymphoma and benign hematologic disorders. I am specialized in the diagnosis of hematological disorders, including acute and chronic leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, B and T-cell lymphomas, Hodgkin lymphoma, cutaneous and orbital lymphomas and benign bone marrow and lymph node disorders. 

Our group has been supported by various funding resources since 2006 and has published 318 original peer-reviewed articles and 56 review articles, many in high- impact journals (Nature Clin Onc Rev, JCO, JAMA, Lancet, Blood, JHO, Leukemia and Clinical Cancer Research). The contributions to the hematology field include the development of novel diagnostic algorithms, molecular and genetic biomarkers for classification of blood cancer, lymphoid neoplasms and lymphoid diseases.



Positions:

Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1984

Zhejiang University (China)

Ph.D. 1995

Lund University (Sweden)

Residency, Pathology

Oregon Health and Science University

Fellowship, Pathology

University of Nebraska Medical Center

Grants:

Genetic and Epigenetic Biomarkers for B-cell Lymphoma

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Genetic and Epigenetic Biomarkers for B-cell Lymphoma

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Genetic and Epigenetic Biomarkers for B-cell Lymphoma

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Hematology & Transfusion Medicine (T32)

Administered By
Medicine, Hematology
Awarded By
National Institutes of Health
Role
Preceptor
Start Date
End Date

Genetic and Epigenetic Biomarkers for B-cell Lymphoma

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Determining clinical course of diffuse large B-cell lymphoma using targeted transcriptome and machine learning algorithms.

Multiple studies have demonstrated that diffuse large B-cell lymphoma (DLBCL) can be divided into subgroups based on their biology; however, these biological subgroups overlap clinically. Using machine learning, we developed an approach to stratify patients with DLBCL into four subgroups based on survival characteristics. This approach uses data from the targeted transcriptome to predict these survival subgroups. Using the expression levels of 180 genes, our model reliably predicted the four survival subgroups and was validated using independent groups of patients. Multivariate analysis showed that this patient stratification strategy encompasses various biological characteristics of DLBCL, and only TP53 mutations remained an independent prognostic biomarker. This novel approach for stratifying patients with DLBCL, based on the clinical outcome of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, can be used to identify patients who may not respond well to these types of therapy, but would otherwise benefit from alternative therapy and clinical trials.
Authors
Albitar, M; Zhang, H; Goy, A; Xu-Monette, ZY; Bhagat, G; Visco, C; Tzankov, A; Fang, X; Zhu, F; Dybkaer, K; Chiu, A; Tam, W; Zu, Y; Hsi, ED; Hagemeister, FB; Huh, J; Ponzoni, M; Ferreri, AJM; Møller, MB; Parsons, BM; van Krieken, JH; Piris, MA; Winter, JN; Li, Y; Xu, B; Young, KH
MLA Citation
Albitar, Maher, et al. “Determining clinical course of diffuse large B-cell lymphoma using targeted transcriptome and machine learning algorithms.Blood Cancer J, vol. 12, no. 2, Feb. 2022, p. 25. Pubmed, doi:10.1038/s41408-022-00617-5.
URI
https://scholars.duke.edu/individual/pub1509429
PMID
35105854
Source
pubmed
Published In
Blood Cancer Journal
Volume
12
Published Date
Start Page
25
DOI
10.1038/s41408-022-00617-5

Novel insights into the genetics and epigenetics of MALT lymphoma unveiled by next generation sequencing analyses.

Authors
Cascione, L; Rinaldi, A; Bruscaggin, A; Tarantelli, C; Arribas, AJ; Kwee, I; Pecciarini, L; Mensah, AA; Spina, V; Chung, EYL; di Bergamo, LT; Dirnhofer, S; Tzankov, A; Miranda, RN; Young, KH; Traverse-Glehen, A; Gaidano, G; Swerdlow, SH; Gascoyne, R; Rabadan, R; Ponzoni, M; Bhagat, G; Rossi, D; Zucca, E; Bertoni, F
MLA Citation
Cascione, Luciano, et al. “Novel insights into the genetics and epigenetics of MALT lymphoma unveiled by next generation sequencing analyses.Haematologica, vol. 104, no. 12, Dec. 2019, pp. e558–61. Pubmed, doi:10.3324/haematol.2018.214957.
URI
https://scholars.duke.edu/individual/pub1511087
PMID
31018978
Source
pubmed
Published In
Haematologica
Volume
104
Published Date
Start Page
e558
End Page
e561
DOI
10.3324/haematol.2018.214957

Reprogrammed marrow adipocytes contribute to myeloma-induced bone disease.

Osteolytic lesions in multiple myeloma are caused by osteoclast-mediated bone resorption and reduced bone formation. A unique feature of myeloma is a failure of bone healing after successful treatment. We observed adipocytes on trabecular bone near the resorbed area in successfully treated patients. Normal marrow adipocytes, when cocultured with myeloma cells, were reprogrammed and produced adipokines that activate osteoclastogenesis and suppress osteoblastogenesis. These adipocytes have reduced expression of peroxisome proliferator-activated receptor γ (PPARγ) mediated by recruitment of polycomb repressive complex 2 (PRC2), which modifies PPARγ promoter methylation at trimethyl lysine-27 histone H3. We confirmed the importance of methylation in the PPARγ promoter by demonstrating that adipocyte-specific knockout of EZH2, a member of the PRC2, prevents adipocyte reprogramming and reverses bone changes in a mouse model. We validated the strong correlation between the frequency of bone lesions and the expression of EZH2 in marrow adipocytes from patients in remission. These results define a role for adipocytes in genesis of myeloma-associated bone disease and that reversal of adipocyte reprogramming has therapeutic implications.
Authors
Liu, H; He, J; Koh, SP; Zhong, Y; Liu, Z; Wang, Z; Zhang, Y; Li, Z; Tam, BT; Lin, P; Xiao, M; Young, KH; Amini, B; Starbuck, MW; Lee, HC; Navone, NM; Davis, RE; Tong, Q; Bergsagel, PL; Hou, J; Yi, Q; Orlowski, RZ; Gagel, RF; Yang, J
MLA Citation
Liu, Huan, et al. “Reprogrammed marrow adipocytes contribute to myeloma-induced bone disease.Sci Transl Med, vol. 11, no. 494, May 2019. Pubmed, doi:10.1126/scitranslmed.aau9087.
URI
https://scholars.duke.edu/individual/pub1511093
PMID
31142679
Source
pubmed
Published In
Sci Transl Med
Volume
11
Published Date
DOI
10.1126/scitranslmed.aau9087

MYD88 L265P Mutation in Lymphoid Malignancies.

Next-generation sequencing has revealed cancer genomic landscapes, in which over 100 driver genes that, when altered by intragenic mutations, can promote oncogenesis. MYD88 is a driver gene found in hematologic B-cell malignancies. A missense mutation (L265P) changing leucine at position 265 to proline in MYD88 is found in ∼90% of Waldenström macroglobulinemia (WM) cases and in significant portions of activated B-cell diffuse large B-cell lymphomas and IgM monoclonal gammopathy of undetermined significance. Few cancers such as WM have a single amino acid substitution in one gene like MYD88 L265P that occurs in ∼90% of cases, making WM paradigmatic for study of a single causative mutation in oncogenesis. In this review, we summarize the frequency and cancer spectrum of MYD88 L265P and its downstream effects in lymphoid cancers. Malignant B cells with MYD88 L265P are likely transformed from IgM-producing B cells either in response to T-cell-independent antigens or in response to protein antigens before class switching. We also discuss therapeutic strategies that include targeting Bruton tyrosine kinase and other kinases, interfering with the assembly of MYD88 and its interacting partners, and MYD88 L265P-specific peptide-based immunotherapy. Cancer Res; 78(10); 2457-62. ©2018 AACR.
Authors
Yu, X; Li, W; Deng, Q; Li, L; Hsi, ED; Young, KH; Zhang, M; Li, Y
MLA Citation
Yu, Xinfang, et al. “MYD88 L265P Mutation in Lymphoid Malignancies.Cancer Res, vol. 78, no. 10, May 2018, pp. 2457–62. Pubmed, doi:10.1158/0008-5472.CAN-18-0215.
URI
https://scholars.duke.edu/individual/pub1511103
PMID
29703722
Source
pubmed
Published In
Cancer Res
Volume
78
Published Date
Start Page
2457
End Page
2462
DOI
10.1158/0008-5472.CAN-18-0215

Peripheral T-cell lymphoma with unusual clinical presentation of rhabdomyolysis.

Primary extranodal lymphoma is known to occur in nose, gastrointestinal tract, skin, bone, and central nervous system. However, it is extremely rare for primary lymphoma to arise in skeletal muscle. We report a case of a 32-year-old man who presented initially with fever and fatigue. He had a history of alcohol abuse. Laboratory studies and computerized tomography scan showed results consistent with rhabdomyolysis, but the cause of the rhabdomyolysis was undetermined. After biopsy of abdominal skeletal muscle with histologic examination and T-cell receptor gamma chain gene rearrangement analysis, the diagnosis of peripheral T-cell lymphoma was established. After two cycles of the cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide regimen, the patient's symptoms greatly improved. This is the third reported case of peripheral T-cell lymphoma arising in skeletal muscle reported in the literature and which presented clinically with rhabdomyolysis. The alcohol abuse during the clinical course likely worsens the pathologic process of the rhabdomyolysis. Copyright © 2015 John Wiley & Sons, Ltd.
Authors
Liu, Z; Medeiros, LJ; Young, KH
MLA Citation
Liu, Zhiyu, et al. “Peripheral T-cell lymphoma with unusual clinical presentation of rhabdomyolysis.Hematol Oncol, vol. 35, no. 1, Mar. 2017, pp. 125–29. Pubmed, doi:10.1002/hon.2203.
URI
https://scholars.duke.edu/individual/pub1511157
PMID
25921311
Source
pubmed
Published In
Hematol Oncol
Volume
35
Published Date
Start Page
125
End Page
129
DOI
10.1002/hon.2203

Research Areas:

Biomarkers, Pharmacological
Genetic Association Studies
Leukemia
Lymphoblastic leukemia
Lymphoma
Multiple Myeloma