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HOXA9

Monday 17 September 2007

WKP

Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.

In vertebrates, the genes encoding the class of transcription factors called homeobox genes (HOXs ) are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development.

This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation.

This gene is highly similar to the abdominal-B (Abd-B) gene of Drosophila fly. A specific translocation event which causes a fusion between this gene and the NUP98 gene has been associated with myeloid leukemogenesis.

As HOXA9 dysfunction has been implicated in acute myeloid leukemia, and expression of the gene has been shown to differ markedly between erythrocyte lineages of different stages of development, the gene is of particular interest from a hematopoietic perspective.

Function

- HOXA9 is a gene essential to myeloid differentiation that is expressed in PICALM-MLLT10 and MLL-rearranged acute leukemias.

- Epigenetic changes that activate Hoxa9 mediate the decline of muscle with age.

Pathology

- overexpression of HOXA9 in tumors

NB: Constitutive activation of tyrosine kinases by mutations or fusions as BCR-ABL1 could be associated with deregulation of transcription factors central to myeloid differentiation (HOXA9 secondary to PICALM-MLLT10).

References

- Sindt A, Deau B, Brahim W, Staal A, Visanica S, Villarese P, Rault JP, Macintyre E, Delabesse E. Acute monocytic leukemia with coexpression of minor BCR-ABL1 and PICALM-MLLT10 fusion genes along with overexpression of HOXA9. Genes Chromosomes Cancer. 2006 Jun;45(6):575-82. PMID: 16518848