The role of HOX genes in malignant myeloid disease.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Eklund
Elizabeth A
EA
The Feinberg School at Northwestern University and Jesse Brown VHA Medical Center, Chicago, Illinois 60611, USA. e-eklund@northwestern.edu
D002869:Chromosome Aberrations; D015973:Gene Expression Regulation, Leukemic; D005801:Genes, Homeobox / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000502:physiology
C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase