Mark J Levis

Summary

Affiliation: Johns Hopkins University
Country: USA

Publications

  1. ncbi request reprint Pediatric AML primary samples with FLT3/ITD mutations are preferentially killed by FLT3 inhibition
    Patrick Brown
    Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA
    Blood 104:1841-9. 2004
  2. ncbi request reprint FLT3 and acute myeloid leukemia: what is the wild type receptor up to?
    Mark Levis
    Department of Oncology, Kimmel Cancer Center at Johns Hopkins, Baltimore, USA
    Haematologica 90:1586. 2005
  3. ncbi request reprint 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
    Steven Knapper
    Department of Haematology, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XW, United Kingdom
    Blood 108:3262-70. 2006
  4. pmc Phospho-specific flow: fixating on the target
    Mark Levis
    Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
    Clin Cancer Res 18:1493-5. 2012
  5. pmc Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
    Mark Levis
    Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
    Blood 117:3294-301. 2011
  6. pmc Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitors
    Mark Levis
    Kimmel Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA
    Blood 108:3477-83. 2006
  7. pmc Internal tandem duplications of the FLT3 gene are present in leukemia stem cells
    Mark Levis
    Blood 106:673-80. 2005
  8. ncbi request reprint Recent advances in the development of small-molecule inhibitors for the treatment of acute myeloid leukemia
    Mark Levis
    The Kimmel Cancer Center, Johns Hopkins University, Department of Oncology, Baltimore, Maryland, USA
    Curr Opin Hematol 12:55-61. 2005
  9. ncbi request reprint In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important to achieve synergistic cytotoxic effects
    Mark Levis
    Department of Oncology, Baltimore, MD 21231, USA
    Blood 104:1145-50. 2004
  10. pmc Phase 1 dose-escalation trial of clofarabine followed by escalating dose of fractionated cyclophosphamide in adults with relapsed or refractory acute leukaemias
    Amer M Zeidan
    Division of Hematologic Malignancies, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
    Br J Haematol 158:198-207. 2012

Research Grants

Collaborators

Detail Information

Publications44

  1. ncbi request reprint Pediatric AML primary samples with FLT3/ITD mutations are preferentially killed by FLT3 inhibition
    Patrick Brown
    Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA
    Blood 104:1841-9. 2004
    ..Clinical testing of FLT3 inhibitors as molecularly targeted agents for the improvement of outcome of pediatric AML patients is warranted...
  2. ncbi request reprint FLT3 and acute myeloid leukemia: what is the wild type receptor up to?
    Mark Levis
    Department of Oncology, Kimmel Cancer Center at Johns Hopkins, Baltimore, USA
    Haematologica 90:1586. 2005
  3. ncbi request reprint 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
    Steven Knapper
    Department of Haematology, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XW, United Kingdom
    Blood 108:3262-70. 2006
    ..Further evaluation of this compound, in combination with cytotoxic chemotherapy or other targeted agents, is warranted in both FLT3 mutant and wild-type patients...
  4. pmc Phospho-specific flow: fixating on the target
    Mark Levis
    Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
    Clin Cancer Res 18:1493-5. 2012
    ..The problem remains as to how to confirm that the target is actually being hit in vivo. This report describes the application of phospho-specific flow cytometry to establish in vivo target inhibition in real time...
  5. pmc Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
    Mark Levis
    Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
    Blood 117:3294-301. 2011
    ..This study is registered at www.clinicaltrials.gov as #NCT00079482...
  6. pmc Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitors
    Mark Levis
    Kimmel Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA
    Blood 108:3477-83. 2006
    ..Additionally, our results suggest that nonselectivity may constitute an important component of the cytotoxic effect of FLT3 inhibitors in FLT3-mutant AML...
  7. pmc Internal tandem duplications of the FLT3 gene are present in leukemia stem cells
    Mark Levis
    Blood 106:673-80. 2005
    ..Taken together, these experiments establish that the FLT3/ITD mutations are present in leukemia stem cells, and that FLT3 inhibitors may have activity against these cells...
  8. ncbi request reprint Recent advances in the development of small-molecule inhibitors for the treatment of acute myeloid leukemia
    Mark Levis
    The Kimmel Cancer Center, Johns Hopkins University, Department of Oncology, Baltimore, Maryland, USA
    Curr Opin Hematol 12:55-61. 2005
    ..These compounds are typically targeted against components of the tyrosine kinase-Ras-Map kinase pathway that have been activated by mutation...
  9. ncbi request reprint In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important to achieve synergistic cytotoxic effects
    Mark Levis
    Department of Oncology, Baltimore, MD 21231, USA
    Blood 104:1145-50. 2004
    ..These results should be considered when designing trials combining chemotherapy with each of the FLT3 inhibitors currently in clinical development...
  10. pmc Phase 1 dose-escalation trial of clofarabine followed by escalating dose of fractionated cyclophosphamide in adults with relapsed or refractory acute leukaemias
    Amer M Zeidan
    Division of Hematologic Malignancies, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
    Br J Haematol 158:198-207. 2012
    ..In summary, the CLO-CYx4 regimen was well tolerated and had activity in patients with RRAL, especially relapsed ALL. Therefore, CLO-CYx4 can be considered a salvage therapy for adults with RRALs, and warrants further investigations...
  11. pmc Phase 1 and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias
    Judith E Karp
    Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231 1000, USA
    Blood 117:3302-10. 2011
    ..This clinical trial is registered at www.clinicaltrials.gov as #NCT00470197...
  12. ncbi request reprint Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia
    Judith E Karp
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231 1000, USA
    Clin Cancer Res 13:4467-73. 2007
    ..We have now completed a phase II study of sequential flavopiridol, ara-C, and mitoxantrone in 62 adults with poor-risk AML...
  13. pmc Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia
    Judith E Karp
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231 1000, USA
    Leuk Res 34:877-82. 2010
    ..Short OS and DFS correlated with adverse cytogenetics, regardless of age or treatment in CR. The addition of allogeneic BMT in CR translates into long OS and DFS in the majority of eligible patients...
  14. pmc Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia
    Judith E Karp
    Division of Hematologic Malignancies, John Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231 1000, USA
    Blood 119:55-63. 2012
    ..The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively. This study is registered at www.clinicaltrials.gov as #NCT00602771...
  15. ncbi request reprint FLT3/ITD mutation signaling includes suppression of SHP-1
    Peili Chen
    Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231 1000, USA
    J Biol Chem 280:5361-9. 2005
    ..Taken together, these data provide the first evidence that suppression of SHP-1 by FLT3/ITD signaling may be another mechanism contributing to the transformation by FLT3/ITD mutations...
  16. pmc Randomized phase II study of two schedules of flavopiridol given as timed sequential therapy with cytosine arabinoside and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia
    Judith E Karp
    Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland 21231 1000, USA
    Haematologica 97:1736-42. 2012
    ..6 months...
  17. pmc Phase I and pharmacologic trial of cytosine arabinoside with the selective checkpoint 1 inhibitor Sch 900776 in refractory acute leukemias
    Judith E Karp
    Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland 21287, USA
    Clin Cancer Res 18:6723-31. 2012
    ..To extend these findings to the clinical setting, we have conducted a phase I study of cytarabine and SCH 900776...
  18. pmc Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk features
    Judith E Karp
    Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231 1000, USA
    Clin Cancer Res 14:3077-82. 2008
    ..Tipifarnib is an oral farnesyltransferase inhibitor with activity in AML. We conducted a phase II trial of maintenance tipifarnib monotherapy for 48 adults with poor-risk AML in first CR...
  19. ncbi request reprint A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo
    Mark Levis
    Johns Hopkins University School of Medicine, Department of Oncology, Baltimore, MD 21231 1000, USA
    Blood 99:3885-91. 2002
    ..These findings form the basis for a planned clinical trial of CEP-701 in patients with AML harboring FLT3- activating mutations...
  20. pmc 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
    Judith E Karp
    Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD 21231 1000, USA
    Blood 113:4841-52. 2009
    ..These clinical studies are registered at www.clinicaltrials.gov as #NCT00112853...
  21. pmc FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML
    Keith W Pratz
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA
    Blood 115:1425-32. 2010
    ..These results have important implications for the potential therapeutic use of FLT3 inhibitors in that patients with newly diagnosed FLT3-mutant AML might be less likely to respond clinically to highly selective FLT3 inhibition...
  22. ncbi request reprint FLT3 ligand causes autocrine signaling in acute myeloid leukemia cells
    Rui Zheng
    Johns Hopkins University School of Medicine, Oncology, Pediatrica, Baltimore, MD 21231 1000, USA
    Blood 103:267-74. 2004
    ..Taken together, these findings represent strong evidence that wtFLT3 is often constitutively activated in AML and thus, like its mutated form, might contribute to the altered signaling that characterizes leukemogenesis...
  23. ncbi request reprint Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survival
    Kyu Tae Kim
    Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Blood 105:1759-67. 2005
    ..These findings demonstrate that constitutively activated FLT3 signaling up-regulates Pim-1 expression in leukemia cells. This up-regulation contributes to the proliferative and antiapoptotic pathways induced by FLT3 signaling...
  24. ncbi request reprint Constitutive Fms-like tyrosine kinase 3 activation results in specific changes in gene expression in myeloid leukaemic cells
    Kyu Tae Kim
    Department of Oncology, Johns Hopkins University School of Medicine, Bethesda, MD, USA
    Br J Haematol 138:603-15. 2007
    ..The alterations of the gene expression profiles in these cells help to further elucidate the mechanisms of FLT3-mediated leukaemogenesis...
  25. ncbi request reprint Internal tandem duplication mutation of FLT3 blocks myeloid differentiation through suppression of C/EBPalpha expression
    Rui Zheng
    Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231 1000, USA
    Blood 103:1883-90. 2004
    ..Forced expression of C/EBPalpha was also able to overcome FLT3/ITD-mediated differentiation block, further proving the importance of C/EBPalpha in this process...
  26. ncbi request reprint FLT3/ITD expression increases expansion, survival and entry into cell cycle of human haematopoietic stem/progenitor cells
    Li Li
    Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
    Br J Haematol 137:64-75. 2007
    ..CEP-701 may act as a potent therapeutic agent for AML stem cells harbouring FLT3/ITD mutations...
  27. ncbi request reprint Constitutively activated FLT3 phosphorylates BAD partially through pim-1
    Kyu Tae Kim
    Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA
    Br J Haematol 134:500-9. 2006
    ..Our data suggests that Pim-1 is one of the principal kinases mediating the anti-apoptotic function of FLT3/ITD signalling via the phosphorylation of BAD...
  28. pmc A clinically relevant population of leukemic CD34(+)CD38(-) cells in acute myeloid leukemia
    Jonathan M Gerber
    Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Blood 119:3571-7. 2012
    ..ALDH activity appears to distinguish normal from leukemic CD34(+)CD38(-) cells and identifies those AML cells associated with relapse...
  29. ncbi request reprint Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia
    B Douglas Smith
    Departments of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
    Blood 103:3669-76. 2004
    ..Our results show that FLT3 inhibition is associated with clinical activity in AML patients harboring FLT3-activating mutations and indicate that CEP-701 holds promise as a novel, molecularly targeted therapy for this disease...
  30. ncbi request reprint Inhibitory anti-FLT3 antibodies are capable of mediating antibody-dependent cell-mediated cytotoxicity and reducing engraftment of acute myelogenous leukemia blasts in nonobese diabetic/severe combined immunodeficient mice
    Obdulio Piloto
    Department of Oncology and Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Cancer Res 65:1514-22. 2005
    ..Thus, these types of antibodies have the potential to be safe and effective new therapeutic agents for acute myelogenous leukemia and possibly other FLT3-expressing malignancies...
  31. ncbi request reprint FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression
    Patrick Brown
    Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
    Blood 105:812-20. 2005
    ..We conclude that the FLT3 inhibitor CEP-701 effectively suppresses FLT3-driven leukemic cell survival. Clinical testing of CEP-701 as a novel molecularly targeted agent for the treatment of childhood ALL is warranted...
  32. pmc Detection of FLT3 internal tandem duplication and D835 mutations by a multiplex polymerase chain reaction and capillary electrophoresis assay
    Kathleen M Murphy
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA
    J Mol Diagn 5:96-102. 2003
    ..Here we describe the performance characteristics of the assay, assay validation, and our clinical experience using this assay to analyze 147 clinical specimens...
  33. ncbi request reprint Images in clinical medicine. FLT3 Mutation and acute myelogenous leukemia with leukostasis
    Katherine A Thornton
    Johns Hopkins University, School of Medicine, Baltimore, MD 21231, USA
    N Engl J Med 357:1639. 2007
  34. doi request reprint FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance
    Michael R Grunwald
    Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Baltimore, MD 21287, USA
    Int J Hematol 97:683-94. 2013
    ..Understanding the mechanisms of resistance and overcoming these obstacles to target inhibition will be central to the success of these agents...
  35. pmc A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias
    Judith E Karp
    Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231 1000, USA
    Blood 110:1762-9. 2007
    ..This clinical trial is registered with the National Cancer Institute's PDQ at www.clinicaltrials.gov as no. JHOC-J0561...
  36. ncbi request reprint Novel FLT3 tyrosine kinase inhibitors
    Mark Levis
    Johns Hopkins University School of Medicine, Department of Oncology, Baltimore, MD 21231 1000, USA
    Expert Opin Investig Drugs 12:1951-62. 2003
    ..This review summarises these developments and examines these novel agents with regard to both the assays used to characterise them and their clinical potential...
  37. ncbi request reprint Small molecule FLT3 tyrosine kinase inhibitors
    Mark Levis
    Johns Hopkins University School of Medicine, Department of Oncology, Baltimore, Maryland, USA
    Curr Pharm Des 10:1183-93. 2004
    ..In this review, we summarize these developments and compare and contrast these novel agents both with regards to the assays used to characterize them as well as to their clinical potential...
  38. pmc Tandem duplication PCR: an ultrasensitive assay for the detection of internal tandem duplications of the FLT3 gene
    Ming Tseh Lin
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Diagn Mol Pathol 22:149-55. 2013
    ..Further studies using TD-PCR to detect ITD mutants at diagnosis may clarify the clinical significance of those ITD mutants with extremely low allele burden. ..
  39. pmc Bench to bedside targeting of FLT3 in acute leukemia
    Keith W Pratz
    Department of Oncology, Division of Hematologic Malignancies, Sidney Kimmel Cancer Center at Johns Hopkins, 1650 Orleans Street, Baltimore, MD 21231, USA
    Curr Drug Targets 11:781-9. 2010
    ..Several FLT3 inhibitors are currently being tested as single agents and in combination with chemotherapy, and it seems likely that a clinically useful drug will eventually emerge...
  40. pmc Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathways
    Obdulio Piloto
    Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21202, USA
    Blood 109:1643-52. 2007
    ..An approach combining FLT3 TKIs with anti-FLT3 antibodies and/or inhibitors of important pathways downstream of FLT3 may reduce the chances of developing resistance...
  41. pmc A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response
    Keith W Pratz
    Department of Oncology, Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
    Blood 113:3938-46. 2009
    ....
  42. pmc Will newer tyrosine kinase inhibitors have an impact in AML?
    Mark J Levis
    Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA
    Best Pract Res Clin Haematol 23:489-94. 2010
    ..The newer FLT3 inhibitors appear to be more potent in vivo and have shown more promise than the older agents in monotherapy trials...
  43. pmc Incorporating FLT3 inhibitors into acute myeloid leukemia treatment regimens
    Keith Pratz
    Division of Hematologic Malignancies, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
    Leuk Lymphoma 49:852-63. 2008
    ..Ongoing and future studies are aimed at incorporating FLT3 inhibitors into conventional induction and consolidation therapy specifically for patients with FLT3 mutant AML...
  44. ncbi request reprint Kinase inhibitors in leukemia
    Mark Levis
    Johns Hopkins University School of Medicine, Departments of Oncology, Baltimore, Maryland, USA
    Adv Pharmacol 51:1-33. 2004

Research Grants4

  1. Targeting FLT3 as a Novel Specific Therapy for Leukemia
    Mark Levis; Fiscal Year: 2007
    ....
  2. Incorporating FLT3 inhibitors into AML treatment regimens
    Mark J Levis; Fiscal Year: 2010
    ..This proposal is aimed at incorporating a FLT3-targeted therapy into AML treatment so as to improve survival for these patients. ..