Research Topics
Species | Mark J LevisSummaryAffiliation: Johns Hopkins University Country: USA Publications
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Publications
Pediatric AML primary samples with FLT3/ITD mutations are preferentially killed by FLT3 inhibitionPatrick 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...- 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 - 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 chemotherapySteven 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... 
Phospho-specific flow: fixating on the targetMark 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...- Internal tandem duplications of the FLT3 gene are present in leukemia stem cellsMark 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... - Recent advances in the development of small-molecule inhibitors for the treatment of acute myeloid leukemiaMark 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... - Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitorsMark 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... - In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important to achieve synergistic cytotoxic effectsMark 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... - Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapseMark 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... - Phase 1 dose-escalation trial of clofarabine followed by escalating dose of fractionated cyclophosphamide in adults with relapsed or refractory acute leukaemiasAmer 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... - Phase 1 and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemiasJudith 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... - Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemiaJudith 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... - Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemiaJudith 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... - Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemiaJudith 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... - FLT3/ITD mutation signaling includes suppression of SHP-1Peili 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... - Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk featuresJudith 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... - A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivoMark 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... - 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 etoposideJudith 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... - FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AMLKeith 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... - FLT3 ligand causes autocrine signaling in acute myeloid leukemia cellsRui 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... - Constitutively activated FLT3 phosphorylates BAD partially through pim-1Kyu-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... - FLT3/ITD expression increases expansion, survival and entry into cell cycle of human haematopoietic stem/progenitor cellsLi 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... - Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survivalKyu-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... - Constitutive Fms-like tyrosine kinase 3 activation results in specific changes in gene expression in myeloid leukaemic cellsKyu 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... - Internal tandem duplication mutation of FLT3 blocks myeloid differentiation through suppression of C/EBPalpha expressionRui 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... - A clinically relevant population of leukemic CD34(+)CD38(-) cells in acute myeloid leukemiaJonathan 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... - Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemiaB 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... - Detection of FLT3 internal tandem duplication and D835 mutations by a multiplex polymerase chain reaction and capillary electrophoresis assayKathleen 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... - Images in clinical medicine. FLT3 Mutation and acute myelogenous leukemia with leukostasisKatherine A Thornton
Johns Hopkins University, School of Medicine, Baltimore, MD 21231, USA
N Engl J Med 357:1639. 2007 - FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expressionPatrick 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... - 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 miceObdulio 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... - A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemiasJudith 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... - Novel FLT3 tyrosine kinase inhibitorsMark 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... - Small molecule FLT3 tyrosine kinase inhibitorsMark 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... - Bench to bedside targeting of FLT3 in acute leukemiaKeith 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... - A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical responseKeith 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.... - Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathwaysObdulio 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... - 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... - Incorporating FLT3 inhibitors into acute myeloid leukemia treatment regimensKeith 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... - Kinase inhibitors in leukemiaMark Levis
Johns Hopkins University School of Medicine, Departments of Oncology, Baltimore, Maryland, USA
Adv Pharmacol 51:1-33. 2004
Research Grants
- Targeting FLT3 as a Novel Specific Therapy for LeukemiaMark Levis; Fiscal Year: 2007....
- Incorporating FLT3 inhibitors into AML treatment regimensMark 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. ..