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. 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.

We provide 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. 

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)

Publications:

Cross-talk between Myc and p53 in B-cell lymphomas.

Myc and p53 proteins are closely associated with many physiological cellular functions, including immune response and lymphocyte survival, and are expressed in the lymphoid organs, which are sites for the development and activation of B-cell malignancies. Genetic alterations and other mechanisms resulting in constitutive activation, rearrangement, or mutation of MYC and TP53 contribute to the development of lymphomas, progression and therapy resistance by gene dysregulation, activation of downstream anti-apoptotic pathways, and unfavorable microenvironment interactions. The cross-talk between the Myc and p53 proteins contributes to the inferior prognosis in many types of B-cell lymphomas. In this review, we present the physiological roles of Myc and p53 proteins, and recent advances in understanding the pathological roles of Myc, p53, and their cross-talk in lymphoid neoplasms. In addition, we highlight clinical trials of novel agents that directly or indirectly inhibit Myc and/or p53 protein functions and their signaling pathways. Although, to date, these trials have failed to overcome drug resistance, the new results have highlighted the clinical efficiency of targeting diverse mechanisms of action with the goal of optimizing novel therapeutic opportunities to eradicate lymphoma cells.
Authors
Yu, L; Yu, T-T; Young, KH
MLA Citation
Yu, Li, et al. “Cross-talk between Myc and p53 in B-cell lymphomas.Chronic Dis Transl Med, vol. 5, no. 3, Sept. 2019, pp. 139–54. Pubmed, doi:10.1016/j.cdtm.2019.08.001.
URI
https://scholars.duke.edu/individual/pub1427402
PMID
31891126
Source
pubmed
Published In
Chronic Dis Transl Med
Volume
5
Published Date
Start Page
139
End Page
154
DOI
10.1016/j.cdtm.2019.08.001

Identification of hepatitis B virus aetiologic antigens, HBx and Pre-S2, in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) has been reported to have a significant association with the hepatitis B virus (HBV) infection. However, there has been no experimental evidence to determine whether the components of the hepatitis B virus are expressed in lymphoid cells. In this study, we used immunohistochemical methods to explore whether the antigens of hepatitis B virus are expressed in DLBCL lymphoma cells in HBsAg-positive DLBCL patients (HBsAg + DLBCL). HBx antigen was detected in 48.9% of HBsAg + DLBCL patients, and the expression rate of the Pre-S2 antigen was 57.2%. HBx expression was significantly associated with high-level expression of c-Myc, while the Pre-S2 antigen was not. In this study, we demonstrated that HBx antigen and Pre-S2 antigen could be detected in lymphoma cells, and HBx expression was related to c-Myc expression. Our findings provide a strong basis for further study of the HBV-infected DLBCL and molecular mechanism underlying the lymphomagenesis.
Authors
Huang, X; Young, KH; Guo, W; Wang, Y; Wang, X; Xi, Y; Wang, L; Bai, O
MLA Citation
Huang, Xinxing, et al. “Identification of hepatitis B virus aetiologic antigens, HBx and Pre-S2, in diffuse large B-cell lymphoma.Journal of Viral Hepatitis, vol. 27, no. 9, Sept. 2020, pp. 948–50. Epmc, doi:10.1111/jvh.13301.
URI
https://scholars.duke.edu/individual/pub1437431
PMID
32281709
Source
epmc
Published In
Journal of Viral Hepatitis
Volume
27
Published Date
Start Page
948
End Page
950
DOI
10.1111/jvh.13301

Risk of HBV reactivation post CD19-CAR-T cell therapy in DLBCL patients with concomitant chronic HBV infection.

Authors
Yang, C; Xie, M; Zhang, K; Liu, H; Liang, A; Young, KH; Qian, W
MLA Citation
Yang, Chunmei, et al. “Risk of HBV reactivation post CD19-CAR-T cell therapy in DLBCL patients with concomitant chronic HBV infection.Leukemia, June 2020. Pubmed, doi:10.1038/s41375-020-0913-y.
URI
https://scholars.duke.edu/individual/pub1448091
PMID
32533094
Source
pubmed
Published In
Leukemia
Published Date
DOI
10.1038/s41375-020-0913-y

Mutant p53 as an Antigen in Cancer Immunotherapy.

The p53 tumor suppressor plays a pivotal role in cancer and infectious disease. Many oncology treatments are now calling on immunotherapy approaches, and scores of studies have investigated the role of p53 antibodies in cancer diagnosis and therapy. This review summarizes the current knowledge from the preliminary evidence that suggests a potential role of p53 as an antigen in the adaptive immune response and as a key monitor of the innate immune system, thereby speculating on the idea that mutant p53 antigens serve as a druggable targets in immunotherapy. Except in a few cases, the vast majority of published work on p53 antibodies in cancer patients use wild-type p53 as the antigen to detect these antibodies and it is unclear whether they can recognize p53 mutants carried by cancer patients at all. We envision that an antibody targeting a specific mutant p53 will be effective therapeutically against a cancer carrying the exact same mutant p53. To corroborate such a possibility, a recent study showed that a T cell receptor-like (TCLR) antibody, initially made for a wild-type antigen, was capable of discriminating between mutant p53 and wild-type p53, specifically killing more cancer cells expressing mutant p53 than wild-type p53 in vitro and inhibiting the tumour growth of mice injected with mutant p53 cancer cells than mice with wild-type p53 cancer cells. Thus, novel antibodies targeting mutant p53, but not the wild-type isoform, should be pursued in preclinical and clinical studies.
Authors
Sobhani, N; D'Angelo, A; Wang, X; Young, KH; Generali, D; Li, Y
MLA Citation
Sobhani, Navid, et al. “Mutant p53 as an Antigen in Cancer Immunotherapy.Int J Mol Sci, vol. 21, no. 11, June 2020. Pubmed, doi:10.3390/ijms21114087.
URI
https://scholars.duke.edu/individual/pub1447440
PMID
32521648
Source
pubmed
Published In
International Journal of Molecular Sciences
Volume
21
Published Date
DOI
10.3390/ijms21114087

MicroRNAs associated to single drug components of R-CHOP identifies diffuse large B-cell lymphoma patients with poor outcome and adds prognostic value to the international prognostic index.

BACKGROUND:Treatment resistance is a major clinical challenge of diffuse large B-cell lymphoma (DLBCL) where approximately 40% of the patients have refractory disease or relapse. Since DLBCL is characterized by great clinical and molecular heterogeneity, the purpose of the present study was to investigate whether miRNAs associated to single drug components of R-CHOP can improve robustness of individual markers and serve as a prognostic classifier. METHODS:Fifteen DLBCL cell lines were tested for sensitivity towards single drug compounds of the standard treatment R-CHOP: rituximab (R), cyclophosphamide (C), doxorubicin (H), and vincristine (O). For each drug, cell lines were ranked using the area under the dose-response curve and grouped as either sensitive, intermediate or resistant. Baseline miRNA expression data were obtained for each cell line in untreated condition, and differential miRNA expression analysis between sensitive and resistant cell lines identified 43 miRNAs associated to growth response after exposure towards single drugs of R-CHOP. Using the Affymetrix HG-U133 platform, expression levels of miRNA precursors were assessed in 701 diagnostic DLBCL biopsies, and miRNA-panel classifiers predicting disease progression were build using multiple Cox regression or random survival forest. Classifiers were validated and ranked by repeated cross-validation. RESULTS:Prognostic accuracies were assessed by Brier Scores and time-varying area under the ROC curves, which revealed better performance of multivariate Cox models compared to random survival forest models. The Cox model including miR-146a, miR-155, miR-21, miR-34a, and miR-23a~miR-27a~miR-24-2 cluster performed the best and successfully stratified GCB-DLBCL patients into high- and low-risk of disease progression. In addition, combination of the Cox miRNA-panel and IPI substantially increased prognostic performance in GCB classified patients. CONCLUSION:As a proof of concept, we found that expression data of drug associated miRNAs display prognostic utility and adding these to IPI improves prognostic stratification of GCB-DLBCL patients treated with R-CHOP.
Authors
Due, H; Brøndum, RF; Young, KH; Bøgsted, M; Dybkær, K
URI
https://scholars.duke.edu/individual/pub1435311
PMID
32192453
Source
epmc
Published In
Bmc Cancer
Volume
20
Published Date
Start Page
237
DOI
10.1186/s12885-020-6643-8

Research Areas:

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