title: Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival.
abstract: BCL2 and MYC are oncogenes commonly deregulated in lymphomas. Concurrent BCL2 and MYC translocations (BCL2(+)/MYC(+)) were identified in 54 samples by karyotype and/or fluorescence in situ hybridization with the aim of correlating clinical and cytogenetic characteristics to overall survival. BCL2(+)/MYC(+) lymphomas were diagnosed as B-cell lymphoma unclassifiable (BCLU; n = 36) with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL); DLBCL (n = 17), or follicular lymphoma (n = 1). Despite the presence of a t(14;18), 5 cases were BCL2 protein-negative. Nonimmunoglobulin gene/MYC (non-IG/MYC) translocations occurred in 24 of 54 cases (44%) and were highly associated with DLBCL morphology (P < .001). Over a median follow-up of 5.3 years, 6 patients remained in remission and 32 died within 6 months of the MYC(+) rearrangement, irrespective of whether MYC(+) occurred at diagnosis (31 of 54) or transformation (23 of 54; P = .53). A non-IG/MYC translocation partner, absent BCL2 protein expression and treatment with rituximab-based chemotherapy, were associated with a more favorable outcome, but a low International Prognostic Index score and DLBCL morphology were independent predictors of overall survival. A comprehensive cytogenetic analysis of BCL2 and MYC status on all aggressive lymphomas may identify a group of high-risk patients who may benefit from chemotherapeutic regimens that include rituximab and/or BCL2-targeted therapy.
authors: Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors: Nathalie A
authors: NA
authors: Johnson
authors: Kerry J
authors: KJ
authors: Savage
authors: Olga
authors: O
authors: Ludkovski
authors: Susana
authors: S
authors: Ben-Neriah
authors: Ryan
authors: R
authors: Woods
authors: Christian
authors: C
authors: Steidl
authors: Martin J S
authors: MJ
authors: Dyer
authors: Reiner
authors: R
authors: Siebert
authors: John
authors: J
authors: Kuruvilla
authors: Richard
authors: R
authors: Klasa
authors: Joseph M
authors: JM
authors: Connors
authors: Randy D
authors: RD
authors: Gascoyne
authors: Douglas E
authors: DE
authors: Horsman
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics / Q000378:metabolism; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics / Q000378:metabolism; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D000069283:Rituximab; D015996:Survival Rate; D014178:Translocation, Genetic
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D000069283:Rituximab