The role of HOX genes in malignant myeloid disease

Abstract

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. 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. 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.