David Sykes, M.D., Ph.D.

Physician Investigator (Cl)
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
acute myeloid leukemia; cell differentiation; homeodomain proteins; leukemia myeloid; lymphangiectasis; myeloid cells; oncogene proteins fusion; oxidoreductases acting on ch-ch group donors; pancytopenia; paraproteinemias; polycythemia; promyelocyticleukemia; telangiectasis

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. 

I am interested in understanding how HoxA9 establishes differentiation arrest in acute myeloid leukemia. Furthermore, I am interested in identifying new compounds which can overcome this differentiation arrest and which will be active in treating human leukemia.
Research website Publications Clinical Profile
Center for Regenerative Medicine
Simches Building
185 Cambridge Street
Boston, MA 02114-2790