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


RESULTS
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.


CONCLUSIONS
B-cell lymphoma 6 plays a fundamental role in lymphomagenesis and is an excellent therapeutic target for development of improved antilymphoma therapeutic regimens.
Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY 10065, USA.
Weimin
W
Ci
Jose M
JM
Polo
Ari
A
Melnick
D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology*; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic
D051560:Proto-Oncogene Proteins c-bcl-6