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.

Shimin Hu, Zijun Y. Xu-Monette, Alexander Tzankov, Tina Green, Lin Wu, Aarthi Balasubramanyam, Wei min Liu, Carlo Visco, Yong Li, Roberto N. Miranda, Santiago Montes-Moreno, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W L Choi, Xiaoying Zhao & 17 others J. Han van Krieken, Qin Huang, Jooryung Huh, Weiyun Ai, Maurilio Ponzoni, Andrés J M Ferreri, Fan Zhou, Graham W. Slack, Randy D. Gascoyne, Meifeng Tu, Daina Variakojis, Weina Chen, Ronald S. Go, Miguel A. Piris, Michael B. Møller, L. Jeffrey Medeiros, Ken H. Young

Research output: Contribution to journalArticle

360 Citations (Scopus)

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.

Original languageEnglish (US)
JournalBlood
Volume121
Issue number20
DOIs
StatePublished - May 16 2013

Fingerprint

Proto-Oncogene Proteins c-bcl-2
Lymphoma, Large B-Cell, Diffuse
Transcriptome
Gene expression
B-Lymphocytes
Cells
Survival
Gene encoding
Extracellular Matrix Proteins
Cell adhesion
Vincristine
Prednisone
Germinal Center
Doxorubicin
Cyclophosphamide
Genes
Rituximab
Cell Adhesion
Up-Regulation
Down-Regulation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

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. / Hu, Shimin; Xu-Monette, Zijun Y.; Tzankov, Alexander; Green, Tina; Wu, Lin; Balasubramanyam, Aarthi; Liu, Wei min; Visco, Carlo; Li, Yong; Miranda, Roberto N.; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W L; Zhao, Xiaoying; van Krieken, J. Han; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés J M; Zhou, Fan; Slack, Graham W.; Gascoyne, Randy D.; Tu, Meifeng; Variakojis, Daina; Chen, Weina; Go, Ronald S.; Piris, Miguel A.; Møller, Michael B.; Medeiros, L. Jeffrey; Young, Ken H.

In: Blood, Vol. 121, No. 20, 16.05.2013.

Research output: Contribution to journalArticle

Hu, S, Xu-Monette, ZY, Tzankov, A, Green, T, Wu, L, Balasubramanyam, A, Liu, WM, Visco, C, Li, Y, Miranda, RN, Montes-Moreno, S, Dybkaer, K, Chiu, A, Orazi, A, Zu, Y, Bhagat, G, Richards, KL, Hsi, ED, Choi, WWL, Zhao, X, van Krieken, JH, Huang, Q, Huh, J, Ai, W, Ponzoni, M, Ferreri, AJM, Zhou, F, Slack, GW, Gascoyne, RD, Tu, M, Variakojis, D, Chen, W, Go, RS, Piris, MA, Møller, MB, Medeiros, LJ & Young, KH 2013, '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.', Blood, vol. 121, no. 20. https://doi.org/10.1182/blood-2012-10-460063
Hu, Shimin ; Xu-Monette, Zijun Y. ; Tzankov, Alexander ; Green, Tina ; Wu, Lin ; Balasubramanyam, Aarthi ; Liu, Wei min ; Visco, Carlo ; Li, Yong ; Miranda, Roberto N. ; Montes-Moreno, Santiago ; Dybkaer, Karen ; Chiu, April ; Orazi, Attilio ; Zu, Youli ; Bhagat, Govind ; Richards, Kristy L. ; Hsi, Eric D. ; Choi, William W L ; Zhao, Xiaoying ; van Krieken, J. Han ; Huang, Qin ; Huh, Jooryung ; Ai, Weiyun ; Ponzoni, Maurilio ; Ferreri, Andrés J M ; Zhou, Fan ; Slack, Graham W. ; Gascoyne, Randy D. ; Tu, Meifeng ; Variakojis, Daina ; Chen, Weina ; Go, Ronald S. ; Piris, Miguel A. ; Møller, Michael B. ; Medeiros, L. Jeffrey ; Young, Ken H. / 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. In: Blood. 2013 ; Vol. 121, No. 20.
@article{94f3f927c3b3409dbe83bb052afadd64,
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.",
author = "Shimin Hu and Xu-Monette, {Zijun Y.} and Alexander Tzankov and Tina Green and Lin Wu and Aarthi Balasubramanyam and Liu, {Wei min} and Carlo Visco and Yong Li and Miranda, {Roberto N.} and Santiago Montes-Moreno and Karen Dybkaer and April Chiu and Attilio Orazi and Youli Zu and Govind Bhagat and Richards, {Kristy L.} and Hsi, {Eric D.} and Choi, {William W L} and Xiaoying Zhao and {van Krieken}, {J. Han} and Qin Huang and Jooryung Huh and Weiyun Ai and Maurilio Ponzoni and Ferreri, {Andr{\'e}s J M} and Fan Zhou and Slack, {Graham W.} and Gascoyne, {Randy D.} and Meifeng Tu and Daina Variakojis and Weina Chen and Go, {Ronald S.} and Piris, {Miguel A.} and M{\o}ller, {Michael B.} and Medeiros, {L. Jeffrey} and Young, {Ken H.}",
year = "2013",
month = "5",
day = "16",
doi = "10.1182/blood-2012-10-460063",
language = "English (US)",
volume = "121",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "20",

}

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 - Hsi, 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.

PY - 2013/5/16

Y1 - 2013/5/16

N2 - 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.

AB - 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.

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

VL - 121

JO - Blood

JF - Blood

SN - 0006-4971

IS - 20

ER -