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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: 410-614-1005
E-mail address: email@example.com
School of Medicine Address: Cancer Research Building 1, Room 2M44, 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; crenolanib,a selective FLT3 inhibitor with activity against resistant point mutations; 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.
- 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
- 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
- Smith, C.C., Wang, Q., Chin, C.S., Damon, L.E., Levis, M., Perl, A.E., Travers, K.J., Wang, S., Hung, J.P., Zarrinkar, P.P., Schadt, E.E., Kasarskis, A., Kuriyan, J., Shah, N.P. Validation of FLT3/ITD as a therapeutic target in human acute myeloid leukemia. Nature 485(7397):260-3, 2012. Pub Med Reference
- Sexauer, A., Perl, A., Yang, X., Borowitz, M., Gocke, C., Rajkhowa, T., Thiede, C., Frattini, M., Nybakken, G.E., Pratz, K., Karp, J., Smith, B.D., Levis, M. Terminal myeloid differentiation in vivo is induced by FLT3 inhibition in FLT3/ITD AML. Blood 120(20): 4505-14, 2012. Pub Med Reference
- Grunwald, M.R., Levis, M. FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance. Int J Hematol. 97:683-94, 2013. Pub Med Reference
- Ravandi, F., Alattar, M.L., Grunwald, M.R., Rudek, M.A., Rajkhowa, T., Richie, M.A., Pierce, S., Daver, N., Garcia-Manero, G., Faderl, S., Nazha, A., Konopleva, M., Borthakur, G., Burger, J., Kadia, T., Dellasala, S., Andreef, M., Cortes, J., Kantarjian, H., Levis, M. Phase II study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood, 2013 (Epub).
- Cortes, J.E., Kantarjian, H., Foran, J.M., Ghirdaladze, D., Zodelava, M., Borthakur, G., Gammon, G., Trone, D., Armstrong, R.C., James, J., Levis, M. A phase 1 study of Quizartinib (AC220) administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FLT3-ITD status. J Clin Oncol. 2013 (in press).
Other graduate programs in which Dr. Levis participates: