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.

Shimin Hu, Zijun Y. Xu-Monette, Aarthi Balasubramanyam, Ganiraju C. Manyam, Carlo Visco, Alexander Tzankov, Wei min Liu, Roberto N. Miranda, L. Zhang, Santiago Montes-Moreno, Karen Dybkær, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W L Choi, J. Han van Krieken, Qin Huang & 15 others Jooryung Huh, Weiyun Ai, Maurilio Ponzoni, Andrés J M Ferreri, Xiaoying Zhao, Jane N. Winter, Mingzhi Zhang, Ling Li, Michael B. Møller, Miguel A. Piris, Yong Li, Ronald S. Go, Lin Wu, L. Jeffrey Medeiros, Ken H. Young

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2715-2724
Number of pages10
JournalBlood
Volume121
Issue number14
DOIs
Publication statusPublished - Apr 4 2013

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Transcriptome
Gene expression
Cells
Gene encoding
B-Lymphocytes
Lymphocytes
Hodgkin Disease
Chemical activation
Cytokines
Reed-Sternberg Cells
Germinal Center
Survival
Rituximab
Gene Expression Profiling
Lymphocyte Activation
Non-Hodgkin's Lymphoma
Genes
Disease-Free Survival
Up-Regulation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

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. / Hu, Shimin; Xu-Monette, Zijun Y.; Balasubramanyam, Aarthi; Manyam, Ganiraju C.; Visco, Carlo; Tzankov, Alexander; Liu, Wei min; Miranda, Roberto N.; Zhang, L.; Montes-Moreno, Santiago; Dybkær, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W L; Han van Krieken, J.; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés J M; Zhao, Xiaoying; Winter, Jane N.; Zhang, Mingzhi; Li, Ling; Møller, Michael B.; Piris, Miguel A.; Li, Yong; Go, Ronald S.; Wu, Lin; Medeiros, L. Jeffrey; Young, Ken H.

In: Blood, Vol. 121, No. 14, 04.04.2013, p. 2715-2724.

Research output: Contribution to journalArticle

Hu, S, Xu-Monette, ZY, Balasubramanyam, A, Manyam, GC, Visco, C, Tzankov, A, Liu, WM, 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 2013, '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.', Blood, vol. 121, no. 14, pp. 2715-2724. https://doi.org/10.1182/blood-2012-10-461848
Hu, Shimin ; Xu-Monette, Zijun Y. ; Balasubramanyam, Aarthi ; Manyam, Ganiraju C. ; Visco, Carlo ; Tzankov, Alexander ; Liu, Wei min ; Miranda, Roberto N. ; Zhang, L. ; Montes-Moreno, Santiago ; Dybkær, Karen ; Chiu, April ; Orazi, Attilio ; Zu, Youli ; Bhagat, Govind ; Richards, Kristy L. ; Hsi, Eric D. ; Choi, William W L ; Han van Krieken, J. ; Huang, Qin ; Huh, Jooryung ; Ai, Weiyun ; Ponzoni, Maurilio ; Ferreri, Andrés J M ; Zhao, Xiaoying ; Winter, Jane N. ; Zhang, Mingzhi ; Li, Ling ; Møller, Michael B. ; Piris, Miguel A. ; Li, Yong ; Go, Ronald S. ; Wu, Lin ; Medeiros, L. Jeffrey ; Young, Ken H. / 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. In: Blood. 2013 ; Vol. 121, No. 14. pp. 2715-2724.
@article{2f6046c9642642c6bd0ee5f6626f0c11,
title = "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.",
abstract = "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.",
author = "Shimin Hu and Xu-Monette, {Zijun Y.} and Aarthi Balasubramanyam and Manyam, {Ganiraju C.} and Carlo Visco and Alexander Tzankov and Liu, {Wei min} and Miranda, {Roberto N.} and L. Zhang and Santiago Montes-Moreno and Karen Dybk{\ae}r and April Chiu and Attilio Orazi and Youli Zu and Govind Bhagat and Richards, {Kristy L.} and Hsi, {Eric D.} and Choi, {William W L} and {Han van Krieken}, J. and Qin Huang and Jooryung Huh and Weiyun Ai and Maurilio Ponzoni and Ferreri, {Andr{\'e}s J M} and Xiaoying Zhao and Winter, {Jane N.} and Mingzhi Zhang and Ling Li and M{\o}ller, {Michael B.} and Piris, {Miguel A.} and Yong Li and Go, {Ronald S.} and Lin Wu and Medeiros, {L. Jeffrey} and Young, {Ken H.}",
year = "2013",
month = "4",
day = "4",
doi = "10.1182/blood-2012-10-461848",
language = "English",
volume = "121",
pages = "2715--2724",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "14",

}

TY - JOUR

T1 - CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature

T2 - a report from the International DLBCL Rituximab-CHOP Consortium Program Study.

AU - Hu, Shimin

AU - Xu-Monette, Zijun Y.

AU - Balasubramanyam, Aarthi

AU - Manyam, Ganiraju C.

AU - Visco, Carlo

AU - Tzankov, Alexander

AU - Liu, Wei min

AU - Miranda, Roberto N.

AU - Zhang, L.

AU - Montes-Moreno, Santiago

AU - Dybkær, Karen

AU - Chiu, April

AU - Orazi, Attilio

AU - Zu, Youli

AU - Bhagat, Govind

AU - Richards, Kristy L.

AU - Hsi, Eric D.

AU - Choi, William W L

AU - Han van Krieken, J.

AU - Huang, Qin

AU - Huh, Jooryung

AU - Ai, Weiyun

AU - Ponzoni, Maurilio

AU - Ferreri, Andrés J M

AU - Zhao, Xiaoying

AU - Winter, Jane N.

AU - Zhang, Mingzhi

AU - Li, Ling

AU - Møller, Michael B.

AU - Piris, Miguel A.

AU - Li, Yong

AU - Go, Ronald S.

AU - Wu, Lin

AU - Medeiros, L. Jeffrey

AU - Young, Ken H.

PY - 2013/4/4

Y1 - 2013/4/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84878309745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878309745&partnerID=8YFLogxK

U2 - 10.1182/blood-2012-10-461848

DO - 10.1182/blood-2012-10-461848

M3 - Article

VL - 121

SP - 2715

EP - 2724

JO - Blood

JF - Blood

SN - 0006-4971

IS - 14

ER -