Ross L Levine

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. doi request reprint LS104, a non-ATP-competitive small-molecule inhibitor of JAK2, is potently inducing apoptosis in JAK2V617F-positive cells
    Daniel B Lipka
    3rd Medical Department, Johannes Gutenberg University, Langenbeckstrabe 1, 55101 Mainz, Germany
    Mol Cancer Ther 7:1176-84. 2008
  2. doi request reprint JAK2 and MPL mutations in myeloproliferative neoplasms
    Priya Koppikar
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Acta Haematol 119:218-25. 2008
  3. ncbi request reprint JAK-2 mutations and their relevance to myeloproliferative disease
    Ross L Levine
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Curr Opin Hematol 14:43-7. 2007
  4. ncbi request reprint Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera
    Gerlinde Wernig
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 13:311-20. 2008
  5. pmc MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia
    Yana Pikman
    Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 3:e270. 2006
  6. ncbi request reprint Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles
    Stefan Fröhling
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 12:501-13. 2007
  7. pmc FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia
    Benjamin H Lee
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 12:367-80. 2007
  8. pmc The potential for isocitrate dehydrogenase mutations to produce 2-hydroxyglutarate depends on allele specificity and subcellular compartmentalization
    Patrick S Ward
    Cancer Biology and Genetics Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    J Biol Chem 288:3804-15. 2013
  9. pmc Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes
    Rafael Bejar
    Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Clin Oncol 30:3376-82. 2012
  10. pmc Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis
    Andrew J Murphy
    Department of Medicine, Division of Molecular Medicine, Columbia University, New York, New York, USA
    Nat Med 19:586-94. 2013

Detail Information

Publications51

  1. doi request reprint LS104, a non-ATP-competitive small-molecule inhibitor of JAK2, is potently inducing apoptosis in JAK2V617F-positive cells
    Daniel B Lipka
    3rd Medical Department, Johannes Gutenberg University, Langenbeckstrabe 1, 55101 Mainz, Germany
    Mol Cancer Ther 7:1176-84. 2008
    ..To the best of our knowledge, this is the first report on a non-ATP-competitive kinase inhibitor being tested in a clinical trial...
  2. doi request reprint JAK2 and MPL mutations in myeloproliferative neoplasms
    Priya Koppikar
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Acta Haematol 119:218-25. 2008
    ..In this review, we will discuss the genetics of PV, ET and PMF with regard to known somatic mutations, the role of these mutations in hematopoietic transformation and the therapeutic implications of these findings...
  3. ncbi request reprint JAK-2 mutations and their relevance to myeloproliferative disease
    Ross L Levine
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Curr Opin Hematol 14:43-7. 2007
    ..This review focuses on recent studies offering new genetic, biochemical, and functional insight into the role of JAK2V617F in the pathogenesis of these disorders...
  4. ncbi request reprint Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera
    Gerlinde Wernig
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 13:311-20. 2008
    ....
  5. pmc MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia
    Yana Pikman
    Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 3:e270. 2006
    ....
  6. ncbi request reprint Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles
    Stefan Fröhling
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 12:501-13. 2007
    ....
  7. pmc FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia
    Benjamin H Lee
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 12:367-80. 2007
    ..This model provides insights into the consequences of constitutive signaling by an oncogenic tyrosine kinase on hematopoietic progenitor quiescence, function, and cell fate...
  8. pmc The potential for isocitrate dehydrogenase mutations to produce 2-hydroxyglutarate depends on allele specificity and subcellular compartmentalization
    Patrick S Ward
    Cancer Biology and Genetics Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    J Biol Chem 288:3804-15. 2013
    ..The consequences of 2HG elevation are dose-dependent, and the non-equivalent 2HG accumulation resulting from IDH1 and IDH2 mutations may underlie their differential prognosis and prevalence in various cancers...
  9. pmc Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes
    Rafael Bejar
    Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Clin Oncol 30:3376-82. 2012
    ..The identification of patients with greater-than-predicted prognostic risk could influence the selection of therapy and improve the care of patients with lower-risk MDS...
  10. pmc Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis
    Andrew J Murphy
    Department of Medicine, Division of Molecular Medicine, Columbia University, New York, New York, USA
    Nat Med 19:586-94. 2013
    ..HDL infusions may offer a new approach to reducing atherothrombotic events associated with increased platelet production...
  11. pmc JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model
    Thomas Mercher
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 108:2770-9. 2006
    ..These findings provide new insights into pathways and therapeutic targets that contribute to the pathogenesis of AMKL...
  12. pmc Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias
    Omar Abdel-Wahab
    Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Cancer Res 70:447-52. 2010
    ..Given the presence of sAML that have no preexisting JAK2/TET2/ASXL1/IDH1 mutations, our work indicates the existence of other mutations yet to be identified that are necessary for leukemic transformation...
  13. pmc The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model
    Thomas Mercher
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 119:852-64. 2009
    ....
  14. ncbi request reprint Concurrent MPL515 and JAK2V617F mutations in myelofibrosis: chronology of clonal emergence and changes in mutant allele burden over time
    Terra L Lasho
    Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA
    Br J Haematol 135:683-7. 2006
    ..We conclude that MPLW515L/K and JAK2V617F are both early events in MMM and allele burden, rather than the mere presence of these mutations, might be relevant to phenotypic variation in myeloproliferative disorders...
  15. pmc Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcome
    Su Jiang Zhang
    Human Oncology and Pathogenesis Program and Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Blood 119:4480-5. 2012
    ..10-7.00) and multivariate analysis (P<.05; HR, 2.11; 95% CI, 1.01-4.42). These data suggest that SRSF2 mutations contribute to the pathogenesis of LT and may guide novel therapeutic approaches for MPN patients who undergo LT...
  16. pmc Clinical effect of point mutations in myelodysplastic syndromes
    Rafael Bejar
    Department of Medicine, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    N Engl J Med 364:2496-506. 2011
    ..Somatic mutations may influence the clinical phenotype but are not included in current prognostic scoring systems...
  17. ncbi request reprint Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders
    Ross L Levine
    Brigham and Women s Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02155, USA
    Nat Rev Cancer 7:673-83. 2007
    ....
  18. ncbi request reprint MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients
    Animesh D Pardanani
    Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
    Blood 108:3472-6. 2006
    ..Furthermore, MPL mutations may occur concurrently with the JAK2V617F mutation, suggesting that these alleles may have functional complementation in myeloproliferative disease...
  19. pmc Progression of RAS-mutant leukemia during RAF inhibitor treatment
    Margaret K Callahan
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    N Engl J Med 367:2316-21. 2012
    ..Exposure to vemurafenib induced hyperactivation of ERK signaling and proliferation of the leukemic cell population, an effect that was reversed on drug withdrawal...
  20. doi request reprint IDH1 mutations disrupt blood, brain, and barriers
    Alan H Shih
    Human Oncology and Pathogenesis Program, Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cancer Cell 22:285-7. 2012
    ..In the central nervous system, inhibition of collagen and prolyl hydroxylases lead to altered microenvironment and defective angiogenesis...
  21. pmc Metabolism and the leukemic stem cell
    Omar Abdel-Wahab
    Human Oncology and Pathogenesis Program Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Exp Med 207:677-80. 2010
    ..These studies potentially converge on the concept that modulation of reactive oxygen species (ROS) abundance may influence the pathogenesis and treatment of acute myeloid leukemia (AML)...
  22. pmc Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies
    Omar Abdel-Wahab
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Blood 114:144-7. 2009
    ..029). These data indicate that TET2 mutations are observed in different myeloid malignancies and may be important in AML prognosis...
  23. pmc Mutational analysis of therapy-related myelodysplastic syndromes and acute myelogenous leukemia
    Alan H Shih
    Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Haematologica 98:908-12. 2013
    ..5%). Cases with a TP53 mutation or loss of the TP53 locus had a worse overall survival compared to those with wild-type TP53 (8.8 vs. 37.4 months; P=0.0035)...
  24. doi request reprint How do novel molecular genetic markers influence treatment decisions in acute myeloid leukemia?
    Jay P Patel
    Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 20, New York, NY 10065, USA
    Hematology Am Soc Hematol Educ Program 2012:28-34. 2012
    ..We also review the current challenges in translating genomic studies to the clinical setting, which remains a significant challenge and an urgent priority...
  25. pmc Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model
    Gerlinde Wernig
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 107:4274-81. 2006
    ....
  26. ncbi request reprint Advances in the molecular characterization of Philadelphia-negative chronic myeloproliferative disorders
    Yana Pikman
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, USA
    Curr Opin Oncol 19:628-34. 2007
    ..This review focuses on recent studies investigating the role of activated tyrosine kinase signaling in the Philadelphia chromosome negative myeloproliferative disorders...
  27. ncbi request reprint Tumor heterogeneity confounds and illuminates: assessing the implications
    Maria Kleppe
    Human Oncology and Pathogenesis Program and Ross L Levine is also a member of the Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center New York, New York, USA
    Nat Med 20:342-4. 2014
    ....
  28. doi request reprint The role of mutations in epigenetic regulators in myeloid malignancies
    Alan H Shih
    Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA
    Nat Rev Cancer 12:599-612. 2012
    ....
  29. pmc Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways
    Marit Westerterp
    Department of Medicine, Division of Molecular Medicine, Columbia University, New York, NY 10032, USA
    Cell Stem Cell 11:195-206. 2012
    ..Our data identify a role of cholesterol efflux pathways in the control of HSPC mobilization. This may translate into therapeutic strategies for atherosclerosis and hematologic malignancies...
  30. doi request reprint Translocation t(11;17) in de novo myelodysplastic syndrome not associated with acute myeloid or acute promyelocytic leukemia
    Muhamed Baljevic
    Department of Medicine, New York Presbyterian Hospital Weill Cornell Medical Center, New York, NY 10065, USA
    Acta Haematol 129:48-54. 2013
    ....
  31. pmc Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition
    Oliver Weigert
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Exp Med 209:259-73. 2012
    ..Thus, HSP90 is a promising therapeutic target in JAK2-driven cancers, including those with genetic resistance to JAK enzymatic inhibitors...
  32. pmc Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain
    Jeffrey C Lee
    Department of Medical Oncology and Center for Cancer Genome Discovery, Dana Farber Cancer Institute Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 3:e485. 2006
    ..Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy...
  33. pmc Loss of Function of TET2 Cooperates with Constitutively Active KIT in Murine and Human Models of Mastocytosis
    Serena De Vita
    Division of Hematology Oncology, Boston Children s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 9:e96209. 2014
    ..We exploit these findings to validate a combination treatment strategy targeting the epigenetic deregulation caused by loss of TET2 and the constitutively active KIT receptor for the treatment of patients with aggressive SM. ..
  34. pmc TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia
    Takaomi Sanda
    Department of Pediatric Oncology, Children s Hospital, Boston, MA, USA
    Cancer Discov 3:564-77. 2013
    ....
  35. pmc Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia
    Omar Abdel-Wahab
    Human Oncology and Pathogenesis Program, and Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Blood 121:3563-72. 2013
    ..Our understanding of the effects of these mutations on hematopoiesis and potential for therapeutic targeting of specific AML subsets is also reviewed here...
  36. ncbi request reprint Acute myeloid leukemia with translocation t(8;16) presents with features which mimic acute promyelocytic leukemia and is associated with poor prognosis
    Adi Diab
    Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Leuk Res 37:32-6. 2013
    ..These data further support classifying t(8;16) AML as a clinically and molecularly defined subtype of AML marked by characteristic clinical and cytomorphologic features that mimic APL, and is associated with very poor survival...
  37. pmc The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate
    Patrick S Ward
    Abramson Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Cancer Cell 17:225-34. 2010
    ....
  38. doi request reprint Mechanisms of mutations in myeloproliferative neoplasms
    Ross L Levine
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Best Pract Res Clin Haematol 22:489-94. 2009
    ..There are likely additional germline and somatic genetic factors important to the MPN phenotype. Additional studies of large MPN and control cohorts with new techniques will help identify these factors...
  39. doi request reprint Janus kinase mutations
    Ross L Levine
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Semin Oncol 36:S6-11. 2009
    ..However, additional genetic and functional studies are needed to identify the patients that will benefit most from JAK kinase inhibitors...
  40. pmc X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis
    Ross L Levine
    Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 107:4139-41. 2006
    ..In addition, some ET and MMM patients with clonal granulopoiesis have somatic mutations other than JAK2V617F...
  41. pmc EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation
    Wendy Beguelin
    Division of Hematology Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA
    Cancer Cell 23:677-92. 2013
    ..GC B cell (GCB)-type diffuse large B cell lymphomas (DLBCLs) are mostly addicted to EZH2 but not the more differentiated activated B cell (ABC)-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting...
  42. ncbi request reprint Genetics of myeloid malignancies: pathogenetic and clinical implications
    Stefan Fröhling
    Brigham and Women s Hospital, Division of Hematology, Karp Family Research Building, 5th Floor, 1 Blackfan Cir, Boston, MA 02115, USA
    J Clin Oncol 23:6285-95. 2005
    ..Specific examples discussed include RAS mutations, KIT mutations, FLT3 mutations, and core binding factor rearrangements in AML, and JAK2 mutations in polycythemia vera, essential thrombocytosis, and chronic idiopathic myelofibrosis...
  43. pmc A mathematical methodology for determining the temporal order of pathway alterations arising during gliomagenesis
    Yu Kang Cheng
    Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, and Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
    PLoS Comput Biol 8:e1002337. 2012
    ....
  44. pmc Molecular biology of myelodysplastic syndromes
    Alan H Shih
    Human Oncology and Pathogenesis Program and Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, NY 10065, USA
    Semin Oncol 38:613-20. 2011
    ..Recent advances in genomic analysis have identified a number of new genes that may be involved. The molecular description of MDS will lead to better understanding, classification, and treatment of this disease...
  45. pmc The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia
    Ross L Levine
    Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 106:3377-9. 2005
    ..These data indicate that the JAK2V617F allele is present in acute and chronic myeloid malignancies but not in lymphoid malignancies...
  46. pmc Myeloproliferative disorders
    Ross L Levine
    Human Oncology and Pathogenesis Program, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Blood 112:2190-8. 2008
    ..This review will discuss our understanding of the pathogenesis of PV, ET, and PMF, the potential role of JAK2-targeted therapy, and the important unanswered questions that need to be addressed to improve clinical outcome...
  47. pmc The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes
    David P Steensma
    Mayo Clinic and Mayo Clinic College of Medicine, Rochester MN 55905, USA
    Blood 106:1207-9. 2005
    ..The current observation strengthens the specific association between JAK2 V617F and classic MPD, but also suggests an infrequent occurrence in other myeloid disorders...
  48. pmc Highly sensitive method for genomewide detection of allelic composition in nonpaired, primary tumor specimens by use of affymetrix single-nucleotide-polymorphism genotyping microarrays
    Go Yamamoto
    Departments of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
    Am J Hum Genet 81:114-26. 2007
    ..In conclusion, AsCNAR should substantially improve our ability to dissect the complexity of cancer genomes and should contribute to our understanding of the genetic basis of human cancers...
  49. pmc Rare occurrence of the JAK2 V617F mutation in AML subtypes M5, M6, and M7
    Stefan Fröhling
    Blood 107:1242-3. 2006
  50. ncbi request reprint Atrial fibrillation is associated with severe acute ischemic stroke
    Douglas A Dulli
    Department of Neurology, University of Wisconsin Medical School, H6 574, Clinical Science Center, Madison, WI 53792 5132, USA
    Neuroepidemiology 22:118-23. 2003
    ..0005) by multivariate logistic regression. Ischemic stroke associated with AF is typically more severe than ischemic stroke due to other etiologies, and this increased severity is independent of advanced age and other stroke risk factors...
  51. ncbi request reprint The JAK2V617F mutation is acquired secondary to the predisposing alteration in familial polycythaemia vera
    Holger Cario
    Br J Haematol 130:800-1. 2005