Role of histone deacetylases in acute leukemia.
Accumulating evidence points to a connection between cancer and transcriptional control by histone acetylation and deacetylation. This is particularly true with regard to the acute leukemias, many of which are caused by fusion proteins that have been created by chromosomal translocations. Genetic rearrangements that disrupt the retinoic acid receptor-alpha and acute myeloid leukemia-1 genes create fusion proteins that block terminal differentiation of hematopoietic cells by repressing transcription. These fusion proteins interact with nuclear hormone co-repressors, which recruit histone deacetylases to promoters to repress transcription. This finding suggests that proteins within the histone deacetylase complexes may be potential targets for pharmaceutical intervention in many leukemia patients.
Fenrick
R
R
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Hiebert
S W
SW
D000208:Acute Disease; D000818:Animals; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007938:Leukemia / Q000201:enzymology* / Q000235:genetics; D014158:Transcription, Genetic
D006655:Histone Deacetylases