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

Weimin Ci, Jose M. Polo, Ari Melnick

Research output: Contribution to journalReview ArticleResearchpeer-review

61 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)381-390
Number of pages10
JournalCurrent Opinion in Hematology
Volume15
Issue number4
DOIs
Publication statusPublished - Jul 2008
Externally publishedYes

Keywords

  • B-cell lymphoma 6
  • Non-Hodgkin lymphoma
  • Transcription therapy
  • Transcriptional repression

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