The role of HOX genes in malignant myeloid disease

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.