期刊
BLOOD
卷 121, 期 20, 页码 4021-4031出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-10-460063
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资金
- Hematopathology Research Fellowship Award
- Shannon Timmins Leukemia Fellowship Award at The University of Texas MD Anderson Cancer Center
- Cancer Terry Fox program [19001]
- Stiftung zur Krebsbekaempfung Zurich [269]
- The University of Texas MD Anderson Cancer Center Institutional R & D Fund, Institutional Research Grant Award
- MD Anderson Lymphoma Specialized Programs of Research Excellence Development Program Award
- MD Anderson Myeloma Specialized Programs of Research Excellence Research Development Program Award
- Gundersen Lutheran Medical Foundation Award
- MD Anderson Collaborative Funds with Roche Molecular System
- HTG Molecular Diagnostic
- Daiichi Sankyo Pharm
- National Cancer Institute/National Institutes of Health [R01CA138688, 1RC1CA146299, P50CA136411, P50CA142509]
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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