Elizabeth A Eklund1. 1. The Feinberg School at Northwestern University and Jesse Brown VHA Medical Center, Chicago, Illinois 60611, USA. e-eklund@northwestern.edu
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.
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.
Authors: Sebastian Schwind; Kati Maharry; Michael D Radmacher; Krzysztof Mrózek; Kelsi B Holland; Dean Margeson; Susan P Whitman; Christopher Hickey; Heiko Becker; Klaus H Metzeler; Peter Paschka; Claudia D Baldus; Shujun Liu; Ramiro Garzon; Bayard L Powell; Jonathan E Kolitz; Andrew J Carroll; Michael A Caligiuri; Richard A Larson; Guido Marcucci; Clara D Bloomfield Journal: J Clin Oncol Date: 2010-11-15 Impact factor: 44.544