Double‐hit BCL2/MYC translocations in a consecutive cohort of patients with large B‐cell lymphoma – a single centre's experience

Abstract

Concurrent BCL2 and MYC translocations, so called double hit (DH), are a rare finding in large B-cell lymphoma (LBCL). Based on data from retrospective series, DH has been correlated with aggressive clinical behaviour and poor outcome. We conducted a consecutive study of DH incidence and correlation with pathologic and clinical characteristics, including response to Rituximab-containing chemotherapy and survival, in an unselected cohort of patients with LBCL. Translocations involving BCL2 and MYC loci were examined with fluorescent in situ hybridization (FISH) in 157 patients with diffuse large B-cell lymphoma (DLBCL) or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU). The incidence of DH was 11% in the total cohort, 7% of primary LBCL and 21% of transformed LBCL. DH lymphomas were all GCB immunophenotype and were more often BCLU. No clinical characteristics were correlated with the presence of DH, which also had no impact on overall response rate (ORR), relapse rate or overall survival (OS). However, sub-stratification of DH lymphomas by FISH indicated a possible inferior survival related to immunoglobulin MYC translocation partner gene. Screening of patients with BCLU and DLBCL of GCB type for DH BCL2/MYC translocation including MYC translocation partner gene may provide important prognostic information.

MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study

“…16,17 In contrast to BL where MYC is classically translocated within the immunoglobulin (IG) loci, either the IG heavy chain gene (IGH) or more rarely the Ig light chain genes k (IGK) or l (IGL), up to half of MYC-R DLBCL involve non-IG translocation partner genes including BCL6, PAX5, BCL11A, or IKAROS. [17][18][19][20][21] When considering the clinical relevance of MYC-R in DLBCL, there remain several unresolved issues. First, many groups have focused on the prognostic value of MYC gene deregulation in a variety of "aggressive" B-cell lymphomas with controversial results.…”

“…In DLBCL, most studies have reported MYC-R as a strong adverse prognostic factor, [4][5][6][7][8][9][10]22 whereas others failed to demonstrate any significant impact of MYC-R alone on survival. 11,12,19,20 Secondly, DHL have been reported to have an extremely poor prognosis, but most studies were based on the retrospective analysis of patients presenting with very aggressive clinical features, thereby precluding their inclusion in any prospective clinical trials. 16,17,[23][24][25][26][27][28] Finally, the potential role of the MYC translocation partner gene has been addressed in a few recent studies.…”

Bcl-2 Overexpression Inhibits Generation of Intracellular Reactive Oxygen Species and Blocks Adriamycin-induced Apoptosis in Bladder Cancer Cells

“…Induction of apoptosis by diverse stimuli, such as radiation, hyperthermia, growth factor withdrawal, glucocorticoids and multiple classes of chemotherapeutic agents, was inhibited by Bcl-2 (Ailawadhi et al, 2012;Akyurek et al, 2012;Pedersen et al, 2012;Shang et al, 2012;Spampanato et al, 2012). Several models had been proposed to explain the Bcl-2 signaling pathway.…”

B-cell lymphomas with concurrent MYC and BCL2 abnormalities other than translocations behave similarly to MYC/BCL2 double-hit lymphomas

“…[4][5][6][7][8][9][10][11][12][13][14] Numerous case series of MYC/BCL2 double-hit lymphoma are reported in the literature. [15][16][17][18][19][20][21][22][23][24] MYC/ BCL2 DHLs represent B10% of all lymphomas that otherwise resemble diffuse large B-cell lymphoma (DLBCL). 10 Although different studies have focused on different aspects or details of double-hit lymphoma, all studies suggest that patients with these lymphomas commonly have an aggressive clinical course characterized by advanced stage disease, extranodal involvement, and high serum lactate dehydrogenase levels.…”