The role of HOX genes in myeloid leukemogenesis

Abstract

Homeodomain proteins of the Hox family play an important role in regulation of normal hematopoiesis. Substantial evidence also indicates that abnormal Hox protein expression is functionally significant in the pathogenesis of acute myeloid malignancies. The purpose of this review is to outline recent progress in understanding molecular mechanisms involved in Hox regulation of myelopoiesis and myeloid leukemogenesis. Since Hox proteins function as transcription factors, recent studies have focused on identifying Hox target genes. Various approaches to this problem have been taken, including high throughput screening techniques. In these studies, expression profiles of hematopoietic cells overexpressing various Hox proteins have been analyzed to obtain initial information about potential target genes. Identification of common and unique sets of target genes for various Hox proteins will shed light on function and regulation of the Hox code in developing hematopoietic cells. Recent studies have generated some intriguing information about potential Hox target genes involved in myelopoiesis and leukemogenesis. A number of issues regarding Hox protein function are unresolved, however. These issues include determining whether the effects of various Hox proteins are redundant versus antagonistic, identifying mechanisms which regulate Hox protein function and mechanisms by which Hox proteins modulate target gene transcription in a context-dependent manner.