Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma

Qing Ye, Zijun Y. Xu-Monette, Alexandar Tzankov, Lijuan Deng, Xiaoxiao Wang, Ganiraju C. Manyam, Carlo Visco, Santiago Montes-Moreno, Li Zhang, Karen Dybkær, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W.L. Choi, J. Han van Krieken, Jooryung Huh, Maurilio PonzoniAndrés J.M. Ferreri, Ben M. Parsons, Michael B. Møller, Miguel A. Piris, Jane N. Winter, L. Jeffrey Medeiros, van den Shimin Hu, Ken H. Young*

*Corresponding author for this work

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Double-hit B-cell lymphoma is a common designation for a group of tumors characterized by concurrent translocations of MYC and BCL2, BCL6, or other genes. The prognosis of concurrent MYC and BCL6 translocations is not well known. In this study, we assessed rearrangements and expression of MYC, BCL2 and BCL6 in 898 patients with de novo diffuse large B-cell lymphoma treated with standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). Neither BCL6 translocation alone (more frequent in activated B-cell like diffuse large B-cell lymphoma) nor in combination with MYC translocation (observed in 2.0% of diffuse large B-cell lymphoma) predicted poorer survival in diffuse large B-cell lymphoma patients. Diffuse large B-cell lymphoma patients with MYC/BCL6 co-expression did have significantly poorer survival, however, MYC/BCL6 co-expression had no effect on prognosis in the absence of MYC/BCL2 co-expression, and had no additive impact in MYC+/BCL2+ cases. The isolated MYC+/BCL6+/BCL2-subset, more frequent in germinal center B-cell like diffuse large B-cell lymphoma, had significantly better survival compared with the isolated MYC+/BCL2+/BCL6-subset (more frequent in activated B-cell like diffuse large B-cell lymphoma). In summary, diffuse large B-cell lymphoma patients with either MYC/BCL6 rearrangements or MYC/BCL6 co-expression did not always have poorer prognosis; MYC expression levels should be evaluated simultaneously; and double-hit B-cell lymphoma needs to be refined based on the specific genetic abnormalities present in these tumors.

Original languageEnglish (US)
Pages (from-to)2401-2416
Number of pages16
JournalOncotarget
Volume7
Issue number3
DOIs
StatePublished - 2016

Keywords

  • BCL2
  • BCL6
  • Diffuse large B-cell lymphoma
  • Double-hit
  • MYC

ASJC Scopus subject areas

  • Oncology

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    Ye, Q., Xu-Monette, Z. Y., Tzankov, A., Deng, L., Wang, X., Manyam, G. C., Visco, C., Montes-Moreno, S., Zhang, L., Dybkær, K., Chiu, A., Orazi, A., Zu, Y., Bhagat, G., Richards, K. L., Hsi, E. D., Choi, W. W. L., van Krieken, J. H., Huh, J., ... Young, K. H. (2016). Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma. Oncotarget, 7(3), 2401-2416. https://doi.org/10.18632/oncotarget.6262