Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma
Open Access
- 12 November 2015
- journal article
- Published by Impact Journals, LLC in Oncotarget
- Vol. 7 (3), 2401-2416
- https://doi.org/10.18632/oncotarget.6262
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.Keywords
This publication has 52 references indexed in Scilit:
- Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysisBlood, 2014
- High-grade B-cell lymphoma/leukemia associated with t(14;18) and 8q24/MYC rearrangement: a neoplasm of germinal center immunophenotype with poor prognosis.Haematologica, 2007
- Distinctive patterns of BCL6 molecular alterations and their functional consequences in different subgroups of diffuse large B-cell lymphomaLeukemia, 2007
- BCL2 Is a Downstream Effector of MIZ-1 Essential for Blocking c-MYC-induced ApoptosisPublished by Elsevier BV ,2007
- Lymphoid neoplasms associated with concurrent t(14;18) and 8q24/c-MYC translocation generally have a poor prognosisLaboratory Investigation, 2006
- Prediction of Survival in Diffuse Large-B-Cell Lymphoma Based on the Expression of Six GenesNew England Journal of Medicine, 2004
- Coexistent Rearrangements of c-MYC,BCL2, andBCL6 Genes in a Diffuse Large B-Cell LymphomaInternational Journal of Hematology, 2004
- Transcriptional analysis of the B cell germinal center reactionProceedings of the National Academy of Sciences, 2003
- Expression of a single gene, BCL-6, strongly predicts survival in patients with diffuse large B-cell lymphomaBlood, 2001
- Molecular anatomy of BCL6 translocations revealed by long-distance polymerase chain reaction-based assays.2000