B-cell lymphoma 6 and the molecular pathogenesis of diffuse large B-cell lymphoma.
B-cell lymphoma 6 and the molecular pathogenesis of diffuse large B-cell lymphoma.
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DOI：
10.1097/moh.0b013e328302c7df
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发表时间：
2008-07
影响因子：
3.2
通讯作者：
Melnick A
中科院分区：
文献类型：
--
作者：
Ci W;Polo JM;Melnick A
The BCL6 transcriptional repressor is the most commonly involved oncogene in B-cell lymphomas. Sustained expression of BCL6 causes malignant transformation of germinal center (GC) B-cells. Understanding the mechanism of action of BCL6 is crucial for the study of how aberrant transcriptional programming leads to lymphomagenesis and development of targeted anti-lymphoma therapy. Identification of BCL6 target genes indicate a critical role for BCL6 in facilitating a state of physiological genomic instability required for GC B-cells to undergo affinity maturation, and suggest its contribution to several additional cellular functions. The discovery of several layers of counter-regulatory mechanisms reveals how B-cells can control and fine-tune the potentially lymphomagenic actions of BCL6. From the biochemical standpoint, BCL6 can regulate distinct biological pathways through different cofactors. This observation explains how the biological actions of BCL6 can be physiologically controlled through separate mechanisms and affords the means for improved therapeutic targeting. The fact that patients with BCL6-dependent lymphoma can be identified based on gene signatures suggests that therapeutic trials of BCL6 inhibitors could be personalized to these individuals. BCL6 plays a fundamental role in lymphomagenesis and is an excellent therapeutic target for development of improved anti-lymphoma therapeutic regimens.
