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.

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)

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

Publications:

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.

Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1+ tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials. The median duration of response was 16 months in a phase 2 trial. PD-1 blockade has also shown promise in a phase 1 trial of nivolumab in relapsed/refractory B-cell non-Hodgkin lymphomas, including follicular lymphoma, which often displays abundant PD-1 expression on intratumoral T cells, and diffuse large B-cell lymphoma, which variably expresses PD-1 and PD-L1. In primary mediastinal large B-cell lymphoma, which frequently has 9p24.1 alterations, the ORR was 35% in a phase 2 trial of pembrolizumab. In contrast, the ORR with pembrolizumab was 0% in relapsed chronic lymphocytic leukemia (CLL) and 44% in CLL with Richter transformation in a phase 2 trial. T cells from CLL patients have elevated PD-1 expression; CLL PD-1+ T cells can exhibit a pseudo-exhaustion or a replicative senescence phenotype. PD-1 expression was also found in marginal zone lymphoma but not in mantle cell lymphoma, although currently anti-PD-1 clinical trial data are not available. Mechanisms and predictive biomarkers for PD-1 blockade immunotherapy, treatment-related adverse events, hyperprogression, and combination therapies are discussed in the context of B-cell lymphomas.
MLA Citation
Xu-Monette, Zijun Y., et al. “PD-1 expression and clinical PD-1 blockade in B-cell lymphomas..” Blood, vol. 131, no. 1, Jan. 2018, pp. 68–83. Pubmed, doi:10.1182/blood-2017-07-740993.
URI
https://scholars.duke.edu/individual/pub1404998
PMID
29118007
Source
pubmed
Published In
Blood
Volume
131
Published Date
Start Page
68
End Page
83
DOI
10.1182/blood-2017-07-740993

CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study.

CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD30 expression in DLBCL is unknown. Here we report that CD30 expression is a favorable prognostic factor in a cohort of 903 de novo DLBCL patients. CD30 was expressed in ∼14% of DLBCL patients. Patients with CD30(+) DLBCL had superior 5-year overall survival (CD30(+), 79% vs CD30(-), 59%; P = .001) and progression-free survival (P = .003). The favorable outcome of CD30 expression was maintained in both the germinal center B-cell and activated B-cell subtypes. Gene expression profiling revealed the upregulation of genes encoding negative regulators of nuclear factor κB activation and lymphocyte survival, and downregulation of genes encoding B-cell receptor signaling and proliferation, as well as prominent cytokine and stromal signatures in CD30(+) DLBCL patients, suggesting a distinct molecular basis for its favorable outcome. Given the superior prognostic value, unique gene expression signature, and significant value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30(+) DLBCL as a distinct subgroup of DLBCL.
Authors
Hu, S; Xu-Monette, ZY; Balasubramanyam, A; Manyam, GC; Visco, C; Tzankov, A; Liu, W-M; Miranda, RN; Zhang, L; Montes-Moreno, S; Dybkær, K; Chiu, A; Orazi, A; Zu, Y; Bhagat, G; Richards, KL; Hsi, ED; Choi, WWL; Han van Krieken, J; Huang, Q; Huh, J; Ai, W; Ponzoni, M; Ferreri, AJM; Zhao, X; Winter, JN; Zhang, M; Li, L; Møller, MB; Piris, MA; Li, Y; Go, RS; Wu, L; Medeiros, LJ; Young, KH
URI
https://scholars.duke.edu/individual/pub1405050
PMID
23343832
Source
pubmed
Published In
Blood
Volume
121
Published Date
Start Page
2715
End Page
2724
DOI
10.1182/blood-2012-10-461848

Apoptosis signaling and BCL-2 pathways provide opportunities for novel targeted therapeutic strategies in hematologic malignances

Authors
Wu, H; Medeiros, LJ; Young, KH
MLA Citation
Wu, Huanling, et al. “Apoptosis signaling and BCL-2 pathways provide opportunities for novel targeted therapeutic strategies in hematologic malignances.” Blood Reviews, vol. 32, no. 1, Elsevier BV, Jan. 2018, pp. 8–28. Crossref, doi:10.1016/j.blre.2017.08.004.
URI
https://scholars.duke.edu/individual/pub1411472
Source
crossref
Published In
Blood Reviews
Volume
32
Published Date
Start Page
8
End Page
28
DOI
10.1016/j.blre.2017.08.004

Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study.

TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R-CHOP-treated patients with either the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we identified the loop-sheet-helix and L3 motifs in the DNA-binding domain to be the most critical structures for maintaining p53 function. In contrast, TP53 deletion and loss of heterozygosity did not confer worse survival. If gene mutation data are not available, immunohistochemical analysis showing > 50% cells expressing p53 protein is a useful surrogate and was able to stratify patients with significantly different prognoses. We conclude that assessment of TP53 mutation status is important for stratifying R-CHOP-treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies.
Authors
Xu-Monette, ZY; Wu, L; Visco, C; Tai, YC; Tzankov, A; Liu, W-M; Montes-Moreno, S; Dybkaer, K; Chiu, A; Orazi, A; Zu, Y; Bhagat, G; Richards, KL; Hsi, ED; Zhao, XF; Choi, WWL; Zhao, X; van Krieken, JH; Huang, Q; Huh, J; Ai, W; Ponzoni, M; Ferreri, AJM; Zhou, F; Kahl, BS; Winter, JN; Xu, W; Li, J; Go, RS; Li, Y; Piris, MA; Møller, MB; Miranda, RN; Abruzzo, LV; Medeiros, LJ; Young, KH
MLA Citation
Xu-Monette, Zijun Y., et al. “Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study..” Blood, vol. 120, no. 19, Nov. 2012, pp. 3986–96. Pubmed, doi:10.1182/blood-2012-05-433334.
URI
https://scholars.duke.edu/individual/pub1405053
PMID
22955915
Source
pubmed
Published In
Blood
Volume
120
Published Date
Start Page
3986
End Page
3996
DOI
10.1182/blood-2012-05-433334

PD-L1 Expression and Gene Amplification in CD30+Diffuse Large B-Cell Lymphoma (DLBCL): Significance of TP53 Genetic Impact and Clinicopathologic Characteristics

Authors
Rassidakis, G; Miao, Y; Zhang, J; Atsaves, V; Kis, L; Smedby, KE; Li, Y; Xu-Monette, ZY; Young, KH
URI
https://scholars.duke.edu/individual/pub1405118
Source
wos
Published In
Blood
Volume
130
Published Date

Research Areas:

Lymphoma