Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation.
Chromosomal translocations affecting the AML-1 gene are among the most frequent aberrations found in acute leukemia. Because the AML-1 transcription factor is a critical regulator of hematopoeitic cell development, normal homeostasis is disrupted in cells containing these translocations. In this review we describe the mechanisms of transcriptional activation and repression by AML-1 and how this transcriptional control is disrupted by the chromosomal translocations that affect AML-1. Finally, we discuss how the mechanism of transcriptional repression by these chromosomal translocation fusion proteins is a possible target of therapeutic intervention in acute leukemia.
Lutterbach
B
B
Department of Biochemistry, Vanderbilt University, 21st and Garland, Nashville, TN, USA.
Hiebert
S W
SW
D000208:Acute Disease; D002454:Cell Differentiation; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000503:physiopathology; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014178:Translocation, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D014157:Transcription Factors