Mark Levis

Department Affiliation: Primary: Oncology and Medicine, Division of Hematologic Malignancies
Degree: M.D., Ph.D., University of California, San Franciso
Rank: Associate Professor
Telephone Number: 410-502-3629
Fax Number: 410-614-7279
E-mail address: levisma@jhmi.edu
School of Medicine Address: Cancer Research Building 1, Room 243, 1650 Orleans Street, Baltimore, MD 21287

Targeting the FLT3 signaling pathway as a treatment for acute leukemia.

Our broad research goals are to identify and validate novel molecular therapeutic targets in hematopoietic malignancies. We are interested in the identification and pre-clinical development of novel targeted therapies, and, in particular, the “translational” step of this research by using correlative studies to incorporate these novel therapies into existing treatments. Our research is of particular interest to those who wish to be involved in directly translating the results of laboratory bench work into meaningful benefits for patients.

Currently, we are actively involved in the pre-clinical and clinical development of small molecule kinase inhibitors targeting the FLT3 signaling pathway in acute myeloid leukemia. We are interested in 3 compounds in particular- AC220, a FLT3/KIT inhibitor; AR200, a selective FLT3 inhibitor, and PLX3397, another inhibitor of KIT and FLT3. The active projects in the lab include: 1) Characterization of cytotoxic responses of different hematologic malignancies to FLT3 and KIT kinase inhibition; 2) Examination of the interaction of bone marrow stroma and stroma-derived cytokines on the efficacy of these inhibitors; 3) Examination of the differential effect of FLT3 inhibition versus combined FLT3/KIT inhibition on acute myeloid leukemia and bone marrow progenitor cells; and 4) Correlative laboratory studies using blood and marrow samples from patients treated with FLT3 inhibitors, with the aim of developing predictive models for clinical response.

Representative Publications:

Levis, M., Brown, P., Smith, B.D., Stine, A., Pham, R., Stone, R., DeAngelo, D., Galinsky, I., Giles, F., Estey, E., Kantarjian, H., Cohen, P., Wang, Y., Roesel, J., Karp, J., and Small, D. Plasma inhibitory activity (PIA): A pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitors. Blood 108:3477-3483, 2006. Pub Med Reference

Pratz, K.W. and Levis, M. Incorporating FLT3 inhibitors into acute myeloid leukemia treatment regimens. Leuk Lymphoma 49(5):852-863, 2008. Pub Med Reference

Pratz, K.W., Cortes, J., Roboz, G., Rao, N., Arowojolu, O., Stine, A., Shiotsu, Y., Shudo, A., Akinaga, S., Small, D., Karp, J., and Levis, M. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood 113:3938-3946, 2009. Pub Med Reference

Zarrinkar, P.P., Gunawardane, R.N., Cramer, M.D., Gardner, M.F., Brigham, D., Belli, B., Karaman, M.W., Pratz, K.W., Pallares, G., Chao, Q., Sprankle, K.G., Patel, H.K., Levis, M., Armstrong, R.C., James, J., and Bhagwat, S.S. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood 114(14):2984-2992, 2009. Pub Med Reference

Pratz, K.W., Sato, T., Murphy, K.M., Stine, A.. Rajkhowa, T., and Levis, M. FLT3 mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood 115:1425-1432, 2010. Pub Med Reference

Sato, T., Yang, X.C., Knapper, S., White, P., Smith, B.D., Galkin, S., Small, D., Burnett, A., Levis., M. FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo. Blood 117(12):3286-93, 2011. Pub Med Reference

Levis, M., Ravandi, F., Wang, E., Baer, M. et al. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood 117(12):3294-301, 2011. Pub Med Reference

Fathi, A., Levis, M. FLT3 inhibitors: A story of the old and the new. Curr Opin Hematol. 18(2):71-6, 2011. Pub Med Reference

Zheng, R., Bailey, E., Nguyen, B., Yang, X., Piloto, O., Levis, M., Small, D. Further activation of FLT3 mutants by FLT3 ligand. Oncogene 2011 Apr 25. [Epub ahead of print]. Pub Med Reference