Key roles of histone methyltransferase and demethylase in leukemogenesis.
A growing body of evidence has underlined the involvement of histone methyltransferases and demethylases in leukemia development. These findings can be roughly classified into two categories according to their association with leukemia. On the one hand, these histone modifiers are recruited to DNA by specific affinities of aberrantly expressed transcription factors or fusion proteins, and induce chromatin modifications to regulate target gene expression. Epigenetic regulators may function as oncogenes in this context. On the other hand, recent studies have identified inactivating mutations of some key histone modulators in myeloid malignancies and these results suggest that they act as tumor suppressors. Profound understanding of these findings in the two categories will help us consider clinical applications of epigenetic drugs. In this prospect we will review the leukemogenic mechanisms clarified by the epigenetic approach and the current findings on genetic aberrations in each methyltransferase or demethylase, and discuss the potential of medical intervention in leukemia or leukemia stem cells targeting histone modifiers.
Department of Hematology & Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Akihide
A
Yoshimi
Mineo
M
Kurokawa
D000818:Animals; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000201:enzymology* / Q000235:genetics; D008954:Models, Biological; D009154:Mutation
D056466:Histone Demethylases; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase