David Sykes, M.D., Ph.D.
Clinicn Investigator, Asst Prf Cancer Center, Mass General Research Institute |
Assistant Professor of Medicine Harvard Medical School |
Assistant In Medicine Medicine-Hematology/Oncology, Massachusetts General Hospital |
MD UCSD 2004 |
Research Interests
Research Narrative
Acute myeloid leukemia (AML) is a devastating disease with a5-year survival rate of 25%. One success story has been the discovery of drugswhich trigger differentiation in the 10% of patients with acute promyelocyticleukemia. Differentiation therapies, including all-trans retinoic acid, arewell-tolerated and extremely effective, leading to 5-year survival ratesapproaching 80% in the small subset of patients with acute promyelocyticleukemia. Differentiation therapy is unfortunately not available for theremaining 90% of patients with AML.
HoxA9 is a critical mediator of normal hematopoiesis. Theexpression of HoxA9 is normally downregulated as cells mature along the myeloidlineage. The inappropriate expression of HoxA9 has been demonstrated in themajority (>70%) of AML. Furthermore, those leukemias which contain MLLfusion oncoproteins are dependent upon HoxA9 for their proliferation andsurvival. These observations make HoxA9 and its downstream effectors attractivecandidates for drug targeting. The gene targets of HoxA9 and the mechanism bywhich HoxA9 establishes differentiation arrest in leukemia are not known.
dbsykes@mgh.harvard.edu |
Center for Regenerative Medicine Simches Building 185 Cambridge Street Boston, MA 02114-2790 |