TY - JOUR
T1 - 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
T2 - A report from the International DLBCL Rituximab-CHOP Consortium Program
AU - Hu, Shimin
AU - Xu-Monette, Zijun Y.
AU - Tzankov, Alexander
AU - Green, Tina
AU - Wu, Lin
AU - Balasubramanyam, Aarthi
AU - Liu, Wei Min
AU - Visco, Carlo
AU - Li, Yong
AU - Miranda, Roberto N.
AU - Montes-Moreno, Santiago
AU - Dybkaer, Karen
AU - Chiu, April
AU - Orazi, Attilio
AU - Zu, Youli
AU - Bhagat, Govind
AU - Richards, Kristy L.
AU - His, Eric D.
AU - Choi, William W.L.
AU - Zhao, Xiaoying
AU - Van Krieken, J. Han
AU - Huang, Qin
AU - Huh, Jooryung
AU - Ai, Weiyun
AU - Ponzoni, Maurilio
AU - Ferreri, Andrés J.M.
AU - Zhou, Fan
AU - Slack, Graham W.
AU - Gascoyne, Randy D.
AU - Tu, Meifeng
AU - Variakojis, Daina
AU - Chen, Weina
AU - Go, Ronald S.
AU - Piris, Miguel A.
AU - Møller, Michael B.
AU - Medeiros, L. Jeffrey
AU - Young, Ken H.
N1 - Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013/5/16
Y1 - 2013/5/16
N2 - Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal centerB-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, weanalyzed 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, ismore 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.
AB - Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal centerB-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, weanalyzed 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, ismore 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.
UR - http://www.scopus.com/inward/record.url?scp=84879385620&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879385620&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-10-460063
DO - 10.1182/blood-2012-10-460063
M3 - Article
C2 - 23449635
AN - SCOPUS:84879385620
SN - 0006-4971
VL - 121
SP - 4021
EP - 4031
JO - Blood
JF - Blood
IS - 20
ER -