Leukaemogenesis: more than mutant genes.
Acute leukaemias are characterized by recurring chromosomal aberrations and gene mutations that are crucial to disease pathogenesis. It is now evident that epigenetic modifications, including DNA methylation and histone modifications, substantially contribute to the phenotype of leukaemia cells. An additional layer of epigenetic complexity is the pathogenetic role of microRNAs in leukaemias, and their key role in the transcriptional regulation of tumour suppressor genes and oncogenes. The genetic heterogeneity of acute leukaemias poses therapeutic challenges, but pharmacological agents that target components of the epigenetic machinery are promising as a component of the therapeutic arsenal for this group of diseases.
Chen
Jianjun
J
Department of Medicine, University of Chicago, IL 60637, USA.
Odenike
Olatoyosi
O
Rowley
Janet D
JD
D000818:Animals; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D009154:Mutation
D035683:MicroRNAs