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:
Spatially resolved, single cell biomarkers of B cell lymphoma
Administered By
Pathology
Awarded By
Cedars Sinai Medical Center
Role
Principal Investigator
Start Date
End Date
Publications:
Clinicopathologic Features and Genomic Signature of De Novo CD5 + Diffuse Large B-Cell Lymphoma : A Multicenter Collaborative Study.
De novo CD5 + diffuse large B-cell lymphoma (DLBCL) has poor survival in the era of immunochemotherapy. Accurate gene-based typing and prognostic stratification can enhance the development of effective individualized treatments. Therefore, we conducted a multicenter retrospective study to evaluate the clinicopathologic characteristics, genomic profiles, and prognostic parameters of 61 patients with CD5 + DLBCL and 60 patients with CD5 - DLBCL, with the goal of facilitating accurate prognostic stratification and potential individualized treatment strategies. Compared with patients with CD5 - DLBCL, older age, advanced stage, higher incidence of central nervous system involvement, and MYC/BCL-2 and p53 overexpression were more prevalent in CD5 + DLBCL. Most patients with CD5 + DLBCL had lymph nodes with non-germinal center B-cell-like or activated B-cell-like subtype according to immunohistochemistry or Lymph2Cx assay. Next-generation sequencing showed that the proportion of MCD subtype (based on the co-occurrence of MYD88 and CD79B mutations) in the CD5 + DLBCL cohort was higher than that in the CD5 - DLBCL cohort (54.2% vs. 13.0%, P =0.005). Compared with the CD5 - cohort, CD5 + DLBCL patients showed poor 5-year overall survival (70.9% vs. 39.0%, P <0.001). Kaplan-Meier survival analysis indicated that cell of origin, MYC/BCL-2, p53, and BCL-6 expression did not have a prognostic impact on patients with CD5 + DLBCL. Multivariate analysis showed that age above 76 years, advanced stage, higher incidence of central nervous system involvement, and hypoalbuminemia were independent factors for poor prognosis in CD5 + DLBCL patients. In summary, CD5 + DLBCL displays poor prognosis, distinctive clinicopathologic characteristics and predominant genetic features of activated B-cell-like and MCD subtypes with worse survival outcome.
Authors
MLA Citation
Sang, Wei, et al. “Clinicopathologic Features and Genomic Signature of De Novo CD5 + Diffuse Large B-Cell Lymphoma : A Multicenter Collaborative Study.” Am J Surg Pathol, vol. 46, no. 11, Nov. 2022, pp. 1533–44. Pubmed, doi:10.1097/PAS.0000000000001957.
URI
https://scholars.duke.edu/individual/pub1533563
PMID
36006771
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
46
Published Date
Start Page
1533
End Page
1544
DOI
10.1097/PAS.0000000000001957
Clinical characteristics and outcomes of Castleman disease: a multicenter Consortium study of 428 patients with 15-year follow-up.
Castleman disease (CD) has been reported as a group of poorly understood lymphoproliferative disorders, including unicentric CD (UCD) and idiopathic multicentric CD (iMCD) which are human immunodeficiency virus (HIV) negative and human herpes virus 8 (HHV-8) negative. The clinical and independent prognostic factors of CD remain poorly elucidated. We retrospectively collected the clinical information of 428 patients with HIV and HHV-8 negative CD from 12 large medical centers with 15-year follow-up. We analyzed the clinicopathologic features of 428 patients (248 with UCD and 180 with iMCD) with a median age of 41 years. The histology subtypes were hyaline-vascular (HV) histopathology for 215 patients (56.58%) and plasmacytic (PC) histopathology for 165 patients (43.42%). Most patients with UCD underwent surgical excision, whereas the treatment strategies of patients with iMCD were heterogeneous. The outcome for patients with UCD was better than that for patients with iMCD, 5-year overall survival (OS) rates were 95% and 74%, respectively. In further analysis, a multivariate analysis using a Cox regression model revealed that PC subtype, hepatomegaly and/or splenomegaly, hemoglobin ≤ 80 g/L, and albumin ≤ 30 g/L were independent prognostic factors of CD for OS. The model of iMCD revealed that age > 60 years, hepatomegaly and/or splenomegaly, and hemoglobin ≤ 80 g/L were independent risk factors. In UCD, single-factor analysis identified two significant risk factors: hemoglobin ≤ 100 g/L and albumin ≤ 30 g/L. Our study emphasizes the distinction of clinical characteristics between UCD and iMCD. The importance of poor risk factors of different clinical classifications may direct more precise and appropriate treatment strategies.
Authors
Liu, W; Cai, Q; Yu, T; Strati, P; Hagemeister, FB; Zhai, Q; Zhang, M; Li, L; Fang, X; Li, J; Sun, R; Zhang, S; Yang, H; Wang, Z; Qian, W; Iwaki, N; Sato, Y; Oksenhendler, E; Xu-Monette, ZY; Young, KH; Yu, L
MLA Citation
Liu, Wanying, et al. “Clinical characteristics and outcomes of Castleman disease: a multicenter Consortium study of 428 patients with 15-year follow-up.” Am J Cancer Res, vol. 12, no. 9, 2022, pp. 4227–40.
URI
https://scholars.duke.edu/individual/pub1554096
PMID
36225639
Source
pubmed
Published In
American Journal of Cancer Research
Volume
12
Published Date
Start Page
4227
End Page
4240
Targetable vulnerability of deregulated FOXM1/PLK1 signaling axis in diffuse large B cell lymphoma.
FOXM1 is a transcription factor that controls cell cycle regulation, cell proliferation, and differentiation. Overexpression of FOXM1 has been implicated in various cancer types. However, the activation status and functional significance of FOXM1 in diffuse large B cell lymphoma (DLBCL) have not been well investigated. Using proteomic approaches, we discovered that the protein expression levels of FOXM1 and PLK1 were positively correlated in DLBCL cell lines and primary DLBCL. Expression levels of FOXM1 and PLK1 mRNAs were also significantly higher in DLBCL than in normal human B cells and could predict poor prognosis of DLBCL, particularly in patients with germinal center B cell-like (GCB) DLBCL. Furthermore, proteomic studies defined a FOXM1-PLK1 signature that consisted of proteins upstream and downstream of that axis involved in the p38-MAPK-AKT pathway, cell cycle, and DNA damage/repair. Further studies demonstrated a mechanistic function of the FOXM1/PLK1 axis in connection with the DNA damage response pathways regulating the S/G2 checkpoint of the cell cycle. Therapeutic targeting of FOXM1/PLK1 using a FOXM1 or PLK1 inhibitor, as well as other clinically relevant small-molecule inhibitors targeting ATR-CHK1, was highly effective in DLBCL in vitro models. These findings are instrumental for lymphoma drug discovery aiming at the FOXM1/PLK1/ATR/CHK1 axis.
Authors
Yu, F; He, H; Nastoupil, LJ; Xu-Monette, ZY; Pham, K; Liang, Y; Chen, G; Fowler, NH; Yin, CC; Tan, D; Yang, Y; Hu, S; Young, KH; Pham, LV; You, MJ
MLA Citation
Yu, Fang, et al. “Targetable vulnerability of deregulated FOXM1/PLK1 signaling axis in diffuse large B cell lymphoma.” Am J Cancer Res, vol. 12, no. 10, 2022, pp. 4666–79.
URI
https://scholars.duke.edu/individual/pub1556741
PMID
36381323
Source
pubmed
Published In
American Journal of Cancer Research
Volume
12
Published Date
Start Page
4666
End Page
4679
Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry.
BACKGROUND: Patients with follicular lymphoma (FL) who experience disease progression within 24 months (POD24) have inferior outcomes. The tumor immune microenvironment (TIME) plays a crucial role in pathogenesis and progression of follicular lymphoma (FL). However, TIME evolution during progression of disease within 24 months (POD24) is elusive. METHODS: Spatially resolved and single-cell image mass cytometry with a panel of 36 metal-tagged antibodies was used to quantitatively analyze the TIME structure in 13 paired FLs at diagnosis and POD24. RESULTS: Follicles and peri-follicular regions were well dissected in structure. Peri-follicular regions represented a barrier for immune infiltration into the follicles. More FL-cells in the peri-follicular regions suffered CD8+T cells attacks under simultaneous protection of regulatory T cells (Tregs) and/or macrophages compared with that in the follicles irrespective of POD24. During POD24, increased CD163- macrophages with PD-1 ligand upregulation and decreased CD8+T cells with upregulated LAG-3 expression around FL-cells were observed in the follicles. Spatial analyses demonstrated that FL-cells interacted more intimately with macrophages than with Tregs and less with cytotoxic T cells in both peri-follicular regions and follicles during POD24. In comparison, macrophages also cooperated more frequently with Tregs to simultaneously hijack FL-cells, creating an enhanced immunosuppressive environment in both peri-follicular and follicular regions during POD24. CONCLUSIONS: Peri-follicular regions function as a barrier by recruiting both CD8+T cells and immunosuppressive cells, protecting follicular FL-cells from immune attack at diagnosis or POD24. FL-cells reside in a more immune-compromised microenvironment and evade immune cell attacks during POD24. Novel immunotherapeutic approaches harnessing LAG-3, macrophages, and Tregs will be empowered to overcome poor outcomes in patients with FL POD24.
Authors
MLA Citation
Liu, Long, et al. “Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry.” J Hematol Oncol, vol. 15, no. 1, Aug. 2022, p. 115. Pubmed, doi:10.1186/s13045-022-01326-z.
URI
https://scholars.duke.edu/individual/pub1533397
PMID
35996180
Source
pubmed
Published In
Journal of Hematology & Oncology
Volume
15
Published Date
Start Page
115
DOI
10.1186/s13045-022-01326-z
HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin's lymphoma. A total of 10%‒15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog(MYC) and/or B-cell lymphoma-2 (BCL2) translocation or amplification. BCL2 inhibitors have potent anti-tumor effects in DLBCL; however, resistance can be acquired through up-regulation of alternative anti-apoptotic proteins. The histone deacetylase (HDAC) inhibitor chidamide can induce BIM expression, leading to apoptosis of lymphoma cells with good efficacy in refractory recurrent DLBCL. In this study, the synergistic mechanism of chidamide and venetoclax in DLBCL was determined through in vitro and in vivo models. We found that combination therapy significantly reduced the protein levels of MYC, TP53, and BCL2 in activated apoptotic-related pathways in DLBCL cells by increasing BIM levels and inducing cell apoptosis. Moreover, combination therapy regulated expression of multiple transcriptomes in DLBCL cells, involving apoptosis, cell cycle, phosphorylation, and other biological processes, and significantly inhibited tumor growth in DLBCL-bearing xenograft mice. Taken together, these findings verify the in vivo therapeutic potential of chidamide and venetoclax combination therapy in DLBCL, warranting pre-clinical trials for patients with DLBCL.
Authors
Luo, C; Yu, T; Young, KH; Yu, L
MLA Citation
Luo, Cancan, et al. “HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression.” J Zhejiang Univ Sci B, vol. 23, no. 8, Aug. 2022, pp. 666–81. Pubmed, doi:10.1631/jzus.B2200016.
URI
https://scholars.duke.edu/individual/pub1533659
PMID
35953760
Source
pubmed
Published In
J Zhejiang Univ Sci B
Volume
23
Published Date
Start Page
666
End Page
681
DOI
10.1631/jzus.B2200016
Research Areas:
Biomarkers, Pharmacological
Genetic Association Studies
Leukemia
Lymphoblastic leukemia
Lymphoma
Multiple Myeloma
Professor of Pathology
Contact:
1-919-668-7568, 40 Medicine Circle, Durham, NC 27710
40 Duke Medicine Circle, Box #3712 Duhs, Durham, NC 27710