Weimin Ci1, Jose M Polo, Ari Melnick. 1. Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY 10065, USA.
Abstract
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.
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.
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