Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B‐cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab

Abstract

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) are a biologically heterogeneous group in which various gene alterations have been reported. The aim of this study was to investigate the frequency and prognostic impact of BCL2, BCL6, and MYC rearrangements in cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP)-treated DLBCL cases. METHODS: Tissue microarrays were constructed from 239 cases of DLBCL, and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. MYC, BCL2, and BCL6 rearrangements were investigated by interphase fluorescence in situ hybridization on tissue microarrays. Survival analysis was constructed from 145 R-CHOP-treated patients. RESULTS: MYC, BCL2, and BCL6 rearrangements were detected in 14 (6%), 36 (15%), and 69 (29%) of 239 DLBCL patients. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases. Of these, 4 had BCL2 and MYC, 2 had BCL6 and MYC, and 1 had BCL2, BCL6, and MYC rearrangements. The prognosis of these cases was extremely poor, with a median survival of 9 months. MYC rearrangement was associated with significantly worse overall survival (P ¼ .01), especially for the cases with GC phenotype (P ¼ .009). BCL6 rearrangement also predicted significantly shorter overall survival (P ¼ .04), especially for the non-GC phenotype (P ¼ .03). BCL2 rearrangement had no prognostic impact on outcome. International Prognostic Index (P ¼ .004) and MYC rearrangement (P ¼ .009) were independent poor prognostic factors. CONCLUSIONS: Analysis of MYC gene rearrangement along with BCL2 and BCL6 is critical in identifying high-risk patients with poor prognosis. Cancer 2012;118:4173-83.

A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients

“…However, several more recent studies within which R-CHOP-treated patients were analyzed revealed that the cell of origin, i.e. GCB or non-GCB phenotype, had no prognostic impact and no difference in OS was observed [32][33][34]. Discrepancies between studies may be explained by the addition of rituximab to chemotherapy, which may modify the prognostic impact of BCL-2 or BCL-6 protein expressions [33,35,36].…”

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

“…Altogether, there were 14 genetic double-hit and triple-hit cases out of 39 MYC rearranged diffuse large B-cell lymphomas (36%), which is within the range of published series. [14][15][16]20 BCL6/MYC genetic double-hit cases were not associated with any specific clinicopathological parameters or outcome and were not considered further.…”

“…17 More recently, the prognostic significance of MYC translocations has been challenged by the recognition of so-called phenotypic double-hit diffuse large B-cell lymphoma. 14,[18][19][20][21] To date, no study has been sufficiently statistically powered to resolve the current debatable issues regarding MYC aberrations in diffuse large B-cell lymphoma and the significance of genetic MYC single-hits vs double-hits in the context of phenotypic double-hits. The goal of this study was to address the above issues in a large number of patients with de novo diffuse large B-cell lymphoma, who were treated with R-CHOP, and stratified according to cell of origin.…”

Does Fascin Expression in Diffuse Large B-Cell Lymphomas have a Clinical Impact in Patients Treated with Anthracyclin-Based Chemotherapy Plus Rituximab?

“…UHOD Number: 2 Volume: 23 Year: 2013 pact of some of these prognostic factors 7,[16][17][18][19] , while prognostic value of some (i.e. GC, non-GC phenotype) remains controversial.…”

“…7,15 Double-hit and triple-hit lymphomas have had a poor response to R-CHOP therapy. 18 Some markers such as beclin-1 were shown to be the predictors of favorable clinical outcome in patients treated with R-CHOP. 20 Fascin was shown to be a poor prognostic factor in certain epithelial tumors due to its role cell adhesion, cell motility and invasiveness.…”