Roles of the histone acetyltransferase monocytic leukemia zinc finger protein in normal and malignant hematopoiesis

Abstract

Histone-modified enzymes are involved in various cell functions, including proliferation, differentiation, cell death and carcinogenesis. The protein MOZ (monocytic leukemia zinc finger protein) is a Myst (MOZ, Ybf2 (Sas3), Sas2, Tip60)-type histone acetyltranseferase (HAT) that generates fusion genes, such as MOZ-TIF2, MOZ-CBP and MOZ-p300, in acute myeloid leukemia (AML) by chromosomal translocation. MOZ associates with AML1 (RUNX1), PU.1, and p53, and cooperatively activates target gene transcription. Gene targeting in mice has revealed that MOZ is essential for the generation and maintenance of hematopoietic stem cells (HSC) and for the appropriate development of myeloid, erythroid and B-lineage cell progenitors. In AML, MOZ fusion genes lead to repressed differentiation, hyper-proliferation, and self-renewal of myeloid progenitors through deregulation of MOZ-regulated target gene expression. It is therefore necessary to analyze the roles of MOZ and MOZ fusion genes in normal and malignant hematopoiesis to elucidate the mechanisms underlying and develop therapies for MOZ-related AML. © 2008 Japanese Cancer Association.