B-cell lymphoma 6 and the molecular pathogenesis of diffuse large B-cell lymphoma

被引：71

作者：

Ci, Weimin

Polo, Jose M. ^{[2
]}

Melnick, Ari ^{[1
]}

机构：

[1] Weill Cornell Med Coll, Dept Med, Div Hematol Oncol, New York, NY 10065 USA

[2] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA

来源：

CURRENT OPINION IN HEMATOLOGY | 2008年 / 15卷 / 04期

关键词：

B-cell lymphoma 6; non-Hodgkin lymphoma; transcription therapy; transcriptional repression;

D O I：

10.1097/MOH.0b013e328302c7df

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Purpose of review The B-cell lymphoma 6 transcriptional repressor is the most commonly involved oncogene in B-cell lymphomas. Sustained expression of B-cell lymphoma 6 causes malignant transformation of germinal center B cells. Understanding the mechanism of action of B-cell lymphoma 6 is crucial for the study of how aberrant transcriptional programming leads to lymphomagenesis and development of targeted antilymphoma therapy. Recent findings Identification of B-cell lymphoma 6 target genes indicates a critical role for B-cell lymphoma 6 in facilitating a state of physiological genomic instability required for germinal center B cells to undergo affinity maturation, and suggests its contribution to several additional cellular functions. The discovery of several layers of counterregulatory mechanisms reveals how B cells can control and fine-tune the potentially lymphomagenic actions of B-cell lymphoma 6. From the biochemical standpoint, B-cell lymphoma 6 can regulate distinct biological pathways through different cofactors. This observation explains how the biological actions of B-cell lymphoma 6 can be physiologically controlled through separate mechanisms and affords the means for improved therapeutic targeting. The fact that patients with B-cell lymphoma 6-dependent lymphoma can be identified on the basis of gene signatures suggests that therapeutic trials of B-cell lymphoma 6 inhibitors could be personalized to these individuals. Summary B-cell lymphoma 6 plays a fundamental role in lymphomagenesis and is an excellent therapeutic target for development of improved antilymphoma therapeutic regimens.

引用

页码：381 / 390

页数：10

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