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
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
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DOI：
10.1182/blood-2012-10-460063
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发表时间：
2013-05-16
期刊：
影响因子：
20.3
通讯作者：
Young, Ken H.
中科院分区：
文献类型：
--
作者：
Hu, Shimin;Xu-Monette, Zijun Y.;Young, Ken H.
弥漫性大B细胞淋巴瘤(DLBCL)根据基因表达特征分为预后良好的生发中心(GCB)样和不良活化的B细胞(ABC)样亚型。在这项研究中，我们分析了893例接受R-CHOP(利妥昔单抗、环磷酰胺、阿霉素、长春新碱和强的松)治疗的DLBCL患者。我们发现MYC/BCL2蛋白共表达在ABC亚型中更为常见。同时表达MYC/BCL2和不表达MYC/BCL2的DLBCL中，ABC或GCB亚型患者的预后相似。与MYC/BCL2共表达导致两个亚型预后差异的观点一致，在没有MYC/BCL2共表达的情况下，两个亚型之间的基因表达特征没有差异。MYC/BCL2共表达的DLBCL表现为编码细胞外基质蛋白的基因显著下调，这些基因涉及基质沉积/重塑和细胞黏附，而增殖相关基因上调。我们的结论是，MYC/BCL2在DLBCL中的共同表达与侵袭性的临床病程有关，在ABC亚型中更为常见，并与ABC-DLBCL患者的总体预后不良有关。综上所述，数据提示MYC/BCL2共表达比细胞来源分类更能预测R-CHOP治疗的DLBCL患者的预后。
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.