The role of HOX genes in malignant myeloid disease

Curr Opin Hematol. 2007 Mar;14(2):85-9. doi: 10.1097/MOH.0b013e32801684b6.

Abstract

Purpose of review: The Hox family of homeodomain transcription factors plays an important role in regulating definitive hematopoiesis. Recent studies indicate that a common characteristic of poor prognosis acute myeloid leukemia is dysregulated expression of a key group of these Hox proteins. The purpose of this review is to outline recent progress in understanding the role that dysregulation of HOX-gene expression plays in the pathogenesis of myeloid leukemogenesis.

Recent findings: A number of recent studies correlate increased expression of HOXA-genes with poor prognosis cytogenetics in acute myeloid leukemia and mixed lineage leukemia. These studies determine that specific ABD HOXA-genes (HoxA7, 9 and 10) are dysregulated as a group. Many such studies also document co-overexpression of homeodomain proteins of the Meis and Pbx families in poor prognosis leukemia. This is of interest, since Meis and Pbx proteins are common DNA-binding partners for Hox proteins.

Summary: These findings suggest that a key characteristic of poor prognosis acute myeloid leukemia is increased, differentiation-stage inappropriate expression of the Abd HoxA proteins and their DNA-binding partners. Such results suggest that dysregulation of the 'Hox code' is important in the pathogenesis of myeloid malignancy.

Publication types

  • Review

MeSH terms

  • Chromosome Aberrations
  • Gene Expression Regulation, Leukemic
  • Genes, Homeobox / physiology*
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Leukemia, Myeloid / genetics*
  • Myeloid-Lymphoid Leukemia Protein / physiology

Substances

  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase