title: MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab.
abstract: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and "double-hit" DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or CHOP-like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event-free survival (EFS) (P = 0·015 and P = 0·005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0·001) and EFS (P = 0·0017) in patients with the germinal centre B-cell (GCB) type, but not in the non-GCB type. In DLBCL, high co-expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk-adapted therapies.
authors: Department of Pathology, University of Manitoba, Winnipeg, MB, Canada.
authors: Anamarija M
authors: AM
authors: Perry
authors: Yuridia
authors: Y
authors: Alvarado-Bernal
authors: Javier A
authors: JA
authors: Laurini
authors: Lynette M
authors: LM
authors: Smith
authors: Graham W
authors: GW
authors: Slack
authors: King L
authors: KL
authors: Tan
authors: Laurie H
authors: LH
authors: Sehn
authors: Kai
authors: K
authors: Fu
authors: Patricia
authors: P
authors: Aoun
authors: Timothy C
authors: TC
authors: Greiner
authors: Wing C
authors: WC
authors: Chan
authors: Philip J
authors: PJ
authors: Bierman
authors: Robert G
authors: RG
authors: Bociek
authors: James O
authors: JO
authors: Armitage
authors: Julie M
authors: JM
authors: Vose
authors: Randy D
authors: RD
authors: Gascoyne
authors: Dennis D
authors: DD
authors: Weisenburger
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: BCL2; MYC; aggressive lymphoma; diffuse large B-cell lymphoma; double-hit lymphoma