Regulation of lymphocyte cell fate decisions and lymphomagenesis by BCL-6.
Genetic alterations of the BCL-6 gene in mice and man have established BCL-6 as a pivotal regulator of normal differentiation of B and T lymphocytes as well as one of the most frequently translocated oncogenes in human B cell lymphomas. As an oncogene, BCL-6 has not been easy to place into existing paradigms of cellular transformation. Rather, it is likely that the function of BCL-6 as a regulator of lymphocyte differentiation is subverted in BCL-6-induced lymphomas. The lymphomas in which BCL-6 is translocated are all suspected to arise from the germinal center B lymphocyte. Given the selective expression of BCL-6 protein in normal germinal center B lymphocytes and the requirement for BCL-6 in germinal center development, the functions of BCL-6 in normal and malignant B cells are probably intertwined. The BCL-6 protein is a potent transcriptional repressor which presumably controls lymphocyte differentiation and induces lymphomas by regulating the expression of key downstream target genes.
Staudt
L M
LM
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. lstaudt@box-1.nih.gov
Dent
A L
AL
Shaffer
A L
AL
Yu
X
X
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology*; D008223:Lymphoma / Q000209:etiology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051560:Proto-Oncogene Proteins c-bcl-6; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors