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Mark James Levis, MD

Associate Professor of Oncology

See Research on Pubmed

Male
Appointment Phone

410-955-8964

Main Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

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Out-of-State & International Patients +
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Call 410-464-6641 (8a.m. to 6p.m., EST, Mon-Fri)

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Call +1-410-502-0773 (7a.m. to 6p.m., EST, Mon-Fri)

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Titles

  • Associate Professor of Oncology
  • Associate Professor of Medicine

Centers & Institutes

  • Sidney Kimmel Comprehensive Cancer Center

Expertise

Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Lymphoblastic Leukemia, Chronic Myeloid Leukemia, Leukemia, Medical Oncology, Myelodysplastic Syndrome

Research Interests

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

Languages

  • English

Clinical Trial Keywords

  • FLT3 inhibitor
Additional Resources +
  • Education +

    Training

    • University of California San Francisco (San Francisco CA) (1994)
    • University of California San Francisco (San Francisco CA) (1992)

    Residencies

    • Johns Hopkins University School of Medicine / Medicine (Baltimore MD) (1997)

    Fellowships

    • Johns Hopkins University School of Medicine / Oncology (Baltimore MD) (2002)
    • Johns Hopkins University School of Medicine / Medical Oncology (Baltimore MD) (2001)
  • Research & Publications +

    Research Summary

    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.

    Selected Publications View all on PubMed

    1. Brown, P.; Levis, M.; McIntyre, E.; Griesemer, M.; Small, D. Combinations of the FLT3 inhibitor CEP-701 and chemotherapy synergistically kill infant and childhood MLL-rearranged ALL cells in a sequence-dependent manner. Leukemia. 2006 Aug;20(8):1368-1376.
    2. Kim, K.T.; Levis, M.; Small, D. Constitutively activated FLT3 phosphorylates BAD partially through pim-1. Br J Haematol. 2006 Sep;134(5):500-509.
    3. Knapper, S.; Burnett, A.K.; Littlewood, T.; Kell, W.J.; Agrawal, S.; Chopra, R.; Clark, R.; Levis, M.J.; Small, D. A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood. 2006 Nov 15;108(10):3262-3270.
    4. 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.E.; Small, D. Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitors. Blood. 2006 Nov 15;108(10):3477-3483.
    5. Kajiguchi, T.; Chung, E.J.; Lee, S.; Stine, A.; Kiyoi, H.; Naoe, T.; Levis, M.J.; Neckers, L.; Trepel, J.B. FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells. Leukemia. 2007 Dec;21(12):2476-2484.
    6. Karp, J.E.; Ricklis, R.M.; Balakrishnan, K.; Briel, J.; Greer, J.; Gore, S.D.; Smith, B.D.; McDevitt, M.A.; Carraway, H.; Levis, M.J.; Gandhi, V. A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias. Blood. 2007 Sep 15;110(6):1762-1769.
    7. Karp, J.E.; Smith, B.D.; Levis, M.J.; Gore, S.D.; Greer, J.; Hattenburg, C.; Briel, J.; Jones, R.J.; Wright, J.J.; Colevas, A.D. Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia. Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4467-4473.
    8. Kim, K.T.; Baird, K.; Davis, S.; Piloto, O.; Levis, M.; Li, L.; Chen, P.; Meltzer, P.; Small, D. Constitutive Fms-like tyrosine kinase 3 activation results in specific changes in gene expression in myeloid leukaemic cells. Br J Haematol. 2007 Sep;138(5):603-615.
    9. Li, L.; Piloto, O.; Kim, K.T.; Ye, Z.; Nguyen, H.B.; Yu, X.; Levis, M.; Cheng, L.; Small, D. FLT3/ITD expression increases expansion, survival and entry into cell cycle of human haematopoietic stem/progenitor cells. Br J Haematol. 2007 Apr;137(1):64-75.
    10. Piloto, O.; Wright, M.; Brown, P.; Kim, K.T.; Levis, M.; Small, D. Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathways. Blood. 2007 Feb 15;109(4):1643-1652.
    11. Thornton, K.A.; Levis, M. Images in clinical medicine. FLT3 Mutation and acute myelogenous leukemia with leukostasis. N Engl J Med. 2007 Oct 18;357(16):1639.
    12. Karp, J.E.; Smith, B.D.; Gojo, I.; Lancet, J.E.; Greer, J.; Klein, M.; Morris, L.; Levis, M.J.; Gore, S.D.; Wright, J.J.; Garrett-Mayer, E. Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk features. Clin Cancer Res. 2008 May 15;14(10):3077-3082.
    13. Pratz, K.; Levis, M. Incorporating FLT3 inhibitors into acute myeloid leukemia treatment regimens. Leuk Lymphoma. 2008 May;49(5):852-863.
    14. Zeng, Z.; Shi, Y.X.; Samudio, I.J.; Wang, R.Y.; Ling, X.; Frolova, O.; Levis, M.; Rubin, J.B.; Negrin, R.R.; Estey, E.H.; Konoplev, S.; Andreeff, M.; Konopleva, M. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood. 2008 Oct 27.
    15. Karp, J.E.; Flatten, K.; Feldman, E.J.; Greer, J.M.; Loegering, D.A.; Ricklis, R.M.; Morris, L.E.; Ritchie, E.; Smith, B.D.; Ironside, V.; Talbott, T.; Roboz, G.; Le, S.B.; Meng, X.W.; Schneider, P.A.; Dai, N.T.; Adjei, A.A.; Gore, S.D.; Levis, M.J.; Wright, J.J.; Garrett-Mayer, E.; Kaufmann, S.H. Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposide. Blood. 2009 May 14;113(20):4841-4852.
    16. Pratz, K.W.; Cortes, J.; Roboz, G.J.; Rao, N.; Arowojolu, O.; Stine, A.; Shiotsu, Y.; Shudo, A.; Akinaga, S.; Small, D.; Karp, J.E.; Levis, M. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood. 2009 Apr 23;113(17):3938-3946.
    17. Karp, J.E.; Blackford, A.; Smith, B.D.; Alino, K.; Seung, A.H.; Bolanos-Meade, J.; Greer, J.M.; Carraway, H.E.; Gore, S.D.; Jones, R.J.; Levis, M.J.; McDevitt, M.A.; Doyle, L.A.; Wright, J.J. Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Leuk Res. 2010 Jul;34(7):877-882.
    18. Levis, M.J. Will newer tyrosine kinase inhibitors have an impact in AML Best Pract Res Clin Haematol. 2010 Dec;23(4):489-494.
    19. Pratz, K.W.; Cho, E.; Levis, M.J.; Karp, J.E.; Gore, S.D.; McDevitt, M.; Stine, A.; Zhao, M.; Baker, S.D.; Carducci, M.A.; Wright, J.J.; Rudek, M.A.; Smith, B.D. A pharmacodynamic study of sorafenib in patients with relapsed and refractory acute leukemias. Leukemia. 2010 Aug;24(8):1437-1444.
    20. Pratz, K.W.; Levis, M.J. Bench to bedside targeting of FLT3 in acute leukemia. Curr Drug Targets. 2010 Jul;11(7):781-789.
    21. Pratz, K.W.; Sato, T.; Murphy, K.M.; Stine, A.; Rajkhowa, T.; Levis, M. FLT3 mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood. 2010 Dec 10;115(7):1425-1432.
    22. Karp, J.E.; Smith, B.D.; Resar, L.S.; Greer, J.M.; Blackford, A.; Zhao, M.; Moton-Nelson, D.; Alino, K.; Levis, M.J.; Gore, S.D.; Joseph, B.; Carraway, H.; McDevitt, M.A.; Bagain, L.; Mackey, K.; Briel, J.; Doyle, L.A.; Wright, J.J.; Rudek, M.A. Phase I and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood. 2011 Jan 14;Epub 1/18/11.

    Lab

    Dr. Levis laboratory research focuses on the development of molecularly targeted therapies for leukemia. Currently, he is actively involved in the pre-clinical and clinical development of small molecule inhibitors of protein kinase, including FLT3. The research involves studying the biochemical effects of these inhibitors on primary blast samples from leukemia patients. 

  • Academic Affiliations & Courses +

    Graduate Program Affiliation

    Cellular and Molecular Medicine (CMM)

  • Activities & Honors +

    Honors

    Clinical Scholar of the Leukemia and Lymphoma Society
  • Videos & Media +
  • Events +
  • Contact & Locations +

    Locations

    Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
    401 N. Broadway
    Baltimore, MD 21231
    Appointment Phone: 410-955-8964
    Location Map

    Department/Division

    • Oncology - Hematologic Malignancies

    For Research Inquiries Contact

    Cancer Research Building 1, Room 2M44,
    1650 Orleans Street,
    Baltimore, MD 21287

    Telephone Number: 410-502-3629
    Fax Number: 410-614-1005
    E-mail address: levisma@jhmi.edu

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