title: Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets.
abstract: HOXA9 is a homeodomain-containing transcription factor that has an important role in hematopoietic stem cell expansion and is commonly deregulated in acute leukemias. A variety of upstream genetic alterations in acute myeloid leukemia lead to overexpression of HOXA9, which is a strong predictor of poor prognosis. In many cases, HOXA9 has been shown to be necessary for maintaining leukemic transformation; however, the molecular mechanisms through which it promotes leukemogenesis remain elusive. Recent work has established that HOXA9 regulates downstream gene expression through binding at promoter distal enhancers along with a subset of cell-specific cofactor and collaborator proteins. Increasing efforts are being made to identify both the critical cofactors and target genes required for maintaining transformation in HOXA9-overexpressing leukemias. With continued advances in understanding HOXA9-mediated transformation, there is a wealth of opportunity for developing novel therapeutics that would be applicable for greater than 50% of AML with overexpression of HOXA9.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: C T
authors.initials: CT
authors.lastname: Collins
authors.affiliation: Department of Pathology and Laboratory Medicine and Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Hess
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D058990:Molecular Targeted Therapy; D011401:Promoter Regions, Genetic
chemical_list: D018398:Homeodomain Proteins; C097899:homeobox protein HOXA9