title: MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program.
abstract: Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). We show that MYC/BCL2 protein coexpression occurred significantly more commonly in the ABC subtype. Patients with the ABC or GCB subtype of DLBCL had similar prognoses with MYC/BCL2 coexpression and without MYC/BCL2 coexpression. Consistent with the notion that the prognostic difference between the 2 subtypes is attributable to MYC/BCL2 coexpression, there is no difference in gene expression signatures between the 2 subtypes in the absence of MYC/BCL2 coexpression. DLBCL with MYC/BCL2 coexpression demonstrated a signature of marked downregulation of genes encoding extracellular matrix proteins, those involving matrix deposition/remodeling and cell adhesion, and upregulation of proliferation-associated genes. We conclude that MYC/BCL2 coexpression in DLBCL is associated with an aggressive clinical course, is more common in the ABC subtype, and contributes to the overall inferior prognosis of patients with ABC-DLBCL. In conclusion, the data suggest that MYC/BCL2 coexpression, rather than cell-of-origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP.
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Shimin
authors: S
authors: Hu
authors: Zijun Y
authors: ZY
authors: Xu-Monette
authors: Alexander
authors: A
authors: Tzankov
authors: Tina
authors: T
authors: Green
authors: Lin
authors: L
authors: Wu
authors: Aarthi
authors: A
authors: Balasubramanyam
authors: Wei-min
authors: WM
authors: Liu
authors: Carlo
authors: C
authors: Visco
authors: Yong
authors: Y
authors: Li
authors: Roberto N
authors: RN
authors: Miranda
authors: Santiago
authors: S
authors: Montes-Moreno
authors: Karen
authors: K
authors: Dybkaer
authors: April
authors: A
authors: Chiu
authors: Attilio
authors: A
authors: Orazi
authors: Youli
authors: Y
authors: Zu
authors: Govind
authors: G
authors: Bhagat
authors: Kristy L
authors: KL
authors: Richards
authors: Eric D
authors: ED
authors: Hsi
authors: William W L
authors: WW
authors: Choi
authors: Xiaoying
authors: X
authors: Zhao
authors: J Han
authors: JH
authors: van Krieken
authors: Qin
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authors: Huang
authors: Jooryung
authors: J
authors: Huh
authors: Weiyun
authors: W
authors: Ai
authors: Maurilio
authors: M
authors: Ponzoni
authors: Andrés J M
authors: AJ
authors: Ferreri
authors: Fan
authors: F
authors: Zhou
authors: Graham W
authors: GW
authors: Slack
authors: Randy D
authors: RD
authors: Gascoyne
authors: Meifeng
authors: M
authors: Tu
authors: Daina
authors: D
authors: Variakojis
authors: Weina
authors: W
authors: Chen
authors: Ronald S
authors: RS
authors: Go
authors: Miguel A
authors: MA
authors: Piris
authors: Michael B
authors: MB
authors: Møller
authors: L Jeffrey
authors: LJ
authors: Medeiros
authors: Ken H
authors: KH
authors: Young
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D016175:B-Lymphocyte Subsets / Q000145:classification / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007391:International Cooperation; D008213:Lymphocyte Activation / Q000235:genetics; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D016019:Survival Analysis; D059467:Transcriptome; 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