Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets

Oncogene. 2016 Mar 3;35(9):1090-8. doi: 10.1038/onc.2015.174. Epub 2015 Jun 1.


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.

Publication types

  • Review

MeSH terms

  • Carcinogenesis / genetics*
  • Gene Expression Regulation, Leukemic
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Humans
  • Leukemia / genetics*
  • Leukemia / pathology
  • Molecular Targeted Therapy
  • Promoter Regions, Genetic


  • Homeodomain Proteins
  • homeobox protein HOXA9