Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

Zijun Y. Xu-Monette, Bouthaina S. Dabaja, Xiaoxiao Wang, Meifeng Tu, Ganiraju C. Manyam, Alexander Tzankov, Yi Xia, Li Zhang, Ruifang Sun, Carlo Visco, Karen Dybkaer, Lihui Yin, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W.L. Choi, J. Han Van KriekenJooryung Huh, Maurilio Ponzoni, Andrés J.M. Ferreri, Michael B. Møller, Ben M. Parsons, Xiaoying Zhao, Jane N. Winter, Miguel A. Piris, Timothy J. McDonnell, Roberto N. Miranda, Yong Li, L. Jeffrey Medeiros, Ken H. Young*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

MYC dysregulation, including MYC gene rearrangement and Myc protein overexpression, is of increasing clinical importance in diffuse large B-cell lymphoma (DLBCL). However, the roles of MYC and the relative importance of rearrangement vs overexpression remain to be refined. Gaining knowledge about the tumor biology associated with MYC dysregulation is important to understand the roles of MYC and MYC-associated biology in lymphomagenesis. In this study, we determined MYC rearrangement status (n=344) and Myc expression (n=535) in a well-characterized DLBCL cohort, individually assessed the clinical and pathobiological features of patients with MYC rearrangement and Myc protein overexpression, and analyzed the prognosis and gene expression profiling signatures associated with these MYC abnormalities in germinal center B-cell-like and activated B-cell-like DLBCL. Our results showed that the prognostic importance of MYC rearrangement vs Myc overexpression is significantly different in germinal center B-cell-like vs activated B-cell-like DLBCL. In germinal center B-cell-like DLBCL, MYC-rearranged germinal center B-cell-like DLBCL patients with Myc overexpression significantly contributed to the clinical, biological, and prognostic characteristics of the overall Myc-overexpressing germinal center B-cell-like DLBCL group. In contrast, in activated B-cell-like DLBCL, the occurrence, clinical and biological features, and prognosis of Myc overexpression were independent of MYC rearrangement. High Myc levels and Myc-independent mechanisms, either tumor cell intrinsic or related to tumor microenvironment, conferred significantly worse survival to MYC-rearranged germinal center B-cell-like DLBCL patients, even among Myc high Bcl-2 high DLBCL patients. This study provides new insight into the tumor biology and prognostic effects associated with MYC dysregulation and suggest that detection of both MYC translocations and evaluation of Myc and Bcl-2 expression is necessary to predict the prognosis of DLBCL patients.

Original languageEnglish (US)
Pages (from-to)1555-1573
Number of pages19
JournalModern Pathology
Volume28
Issue number12
DOIs
StatePublished - Dec 1 2015

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Xu-Monette, Z. Y., Dabaja, B. S., Wang, X., Tu, M., Manyam, G. C., Tzankov, A., Xia, Y., Zhang, L., Sun, R., Visco, C., Dybkaer, K., Yin, L., Chiu, A., Orazi, A., Zu, Y., Bhagat, G., Richards, K. L., Hsi, E. D., Choi, W. W. L., ... Young, K. H. (2015). Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Modern Pathology, 28(12), 1555-1573. https://doi.org/10.1038/modpathol.2015.118