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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.

Publication ,  Journal Article
Hu, S; Xu-Monette, ZY; Tzankov, A; Green, T; Wu, L; Balasubramanyam, A; Liu, W-M; Visco, C; Li, Y; Miranda, RN; Montes-Moreno, S; Dybkaer, K ...
Published in: Blood
May 16, 2013

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.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

May 16, 2013

Volume

121

Issue

20

Start / End Page

4021 / 4031

Location

United States

Related Subject Headings

  • Vincristine
  • Transcriptome
  • Survival Analysis
  • Rituximab
  • Risk Factors
  • Retrospective Studies
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Proteins c-bcl-2
  • Prognosis
  • Prednisone
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hu, S., Xu-Monette, Z. Y., Tzankov, A., Green, T., Wu, L., Balasubramanyam, A., … Young, K. H. (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, 121(20), 4021–4031. https://doi.org/10.1182/blood-2012-10-460063
Hu, Shimin, Zijun Y. Xu-Monette, Alexander Tzankov, Tina Green, Lin Wu, Aarthi Balasubramanyam, Wei-min Liu, et al. “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 121, no. 20 (May 16, 2013): 4021–31. https://doi.org/10.1182/blood-2012-10-460063.
Hu S, Xu-Monette ZY, Tzankov A, Green T, Wu L, Balasubramanyam A, Liu W-M, 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. 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. 2013 May 16;121(20):4021–4031.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

May 16, 2013

Volume

121

Issue

20

Start / End Page

4021 / 4031

Location

United States

Related Subject Headings

  • Vincristine
  • Transcriptome
  • Survival Analysis
  • Rituximab
  • Risk Factors
  • Retrospective Studies
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Proteins c-bcl-2
  • Prognosis
  • Prednisone