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, Li 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 HuangJooryung 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

143 Scopus citations

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 CD301 DLBCL had superior 5-year overall survival (CD301, 79% vs CD30-, 59%; P 5 .001) and progression-free survival (P 5 .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 kB activation and lymphocyte survival, and downregulation of genes encoding B-cell receptor signaling and proliferation, as well as prominent cytokine and stromal signatures in CD301 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 CD301 DLBCL as a distinct subgroup of DLBCL.

Original languageEnglish (US)
Pages (from-to)2715-2724
Number of pages10
JournalBlood
Volume121
Issue number14
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Hu, S., Xu-Monette, Z. Y., Balasubramanyam, A., Manyam, G. C., Visco, C., Tzankov, A., Liu, W. M., Miranda, R. N., Zhang, L., Montes-Moreno, S., Dybkær, K., Chiu, A., Orazi, A., Zu, Y., Bhagat, G., Richards, K. L., Hsi, E. D., Choi, W. W. L., Van Krieken, J. H., ... Young, K. H. (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, 121(14), 2715-2724. https://doi.org/10.1182/blood-2012-10-461848