Ross L Levine

Summary

Affiliation: Memorial Sloan-Kettering Cancer Center
Country: USA

Publications

  1. 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
  2. pmc Recent advances in the treatment 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 10065 USA
    F1000 Med Rep 2:55. 2010
  3. pmc Molecular pathogenesis of AML: translating insights to the clinic
    Ross L Levine
    Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA Electronic address
    Best Pract Res Clin Haematol 26:245-8. 2013
  4. pmc An optimized algorithm for detecting and annotating regional differential methylation
    Sheng Li
    Department of Physiology and Biophysics, Weill Cornell Medical College, 1305 York Ave, New York, NY 10065, USA
    BMC Bioinformatics 14:S10. 2013
  5. ncbi request reprint JAK-mutant myeloproliferative neoplasms
    Ross L Levine
    Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Curr Top Microbiol Immunol 355:119-33. 2012
  6. 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
  7. 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
  8. ncbi 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
  9. pmc Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo
    Omar Abdel-Wahab
    Human Oncology and Pathogenesis Program, 2 Leukemia Service, 3 Gerstner Sloan Kettering Graduate School of Biomedical Sciences, and 4 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065
    J Exp Med 210:2641-59. 2013
  10. pmc ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression
    Omar Abdel-Wahab
    Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    Cancer Cell 22:180-93. 2012

Detail Information

Publications85

  1. 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)...
  2. pmc Recent advances in the treatment 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 10065 USA
    F1000 Med Rep 2:55. 2010
    ..Lastly, we review a recent assessment of the role of allogeneic hematopoietic stem cell transplantation in AML in first complete remission...
  3. pmc Molecular pathogenesis of AML: translating insights to the clinic
    Ross L Levine
    Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA Electronic address
    Best Pract Res Clin Haematol 26:245-8. 2013
    ..Furthermore, this understanding is therapeutically relevant. Rapid and accurate targeted DNA sequencing will identify mutations of prognostic and therapeutic significance and will guide treatment choices in the future. ..
  4. pmc An optimized algorithm for detecting and annotating regional differential methylation
    Sheng Li
    Department of Physiology and Biophysics, Weill Cornell Medical College, 1305 York Ave, New York, NY 10065, USA
    BMC Bioinformatics 14:S10. 2013
    ....
  5. ncbi request reprint JAK-mutant myeloproliferative neoplasms
    Ross L Levine
    Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Curr Top Microbiol Immunol 355:119-33. 2012
    ....
  6. 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...
  7. 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...
  8. ncbi 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...
  9. pmc Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo
    Omar Abdel-Wahab
    Human Oncology and Pathogenesis Program, 2 Leukemia Service, 3 Gerstner Sloan Kettering Graduate School of Biomedical Sciences, and 4 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065
    J Exp Med 210:2641-59. 2013
    ..These findings underscore the importance of Asxl1 in Polycomb group function, development, and hematopoiesis. ..
  10. pmc ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression
    Omar Abdel-Wahab
    Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    Cancer Cell 22:180-93. 2012
    ..We demonstrate that ASXL1 associates with the PRC2, and that loss of ASXL1 in vivo collaborates with NRASG12D to promote myeloid leukemogenesis...
  11. pmc Efficacy of the JAK2 inhibitor INCB16562 in a murine model of MPLW515L-induced thrombocytosis and myelofibrosis
    Priya Koppikar
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Blood 115:2919-27. 2010
    ..However, we did not observe a decrease in the size of the malignant clone in the bone marrow of treated mice at the end of therapy, which suggests that JAK2 inhibitor therapy, by itself, was not curative in this MPN model...
  12. 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
    ....
  13. pmc A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms
    Outi Kilpivaara
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Nat Genet 41:455-9. 2009
    ..We found that JAK2(V617F) is preferentially acquired in cis with the predisposition allele. These data suggest that germline variation is an important contributor to MPN phenotype and predisposition...
  14. pmc Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy
    Priya Koppikar
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 489:155-9. 2012
    ..Consequently, therapies that result in JAK2 degradation retain efficacy in persistent cells and may provide additional benefit to patients with JAK2-dependent malignancies treated with JAK2 inhibitors...
  15. 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...
  16. 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...
  17. pmc IDH mutation impairs histone demethylation and results in a block to cell differentiation
    Chao Lu
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 483:474-8. 2012
    ..Together these data demonstrate that 2HG can inhibit histone demethylation and that inhibition of histone demethylation can be sufficient to block the differentiation of non-transformed cells...
  18. 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...
  19. pmc CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900
    Mithat Gonen
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Blood 120:2297-306. 2012
    ..We conclude that CD25(POS) status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML...
  20. 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...
  21. 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...
  22. 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...
  23. pmc Notch pathway activation targets AML-initiating cell homeostasis and differentiation
    Camille Lobry
    Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA
    J Exp Med 210:301-19. 2013
    ..These data demonstrate a novel tumor suppressor role for Notch signaling in AML and elucidate the potential therapeutic use of Notch receptor agonists in the treatment of this devastating leukemia...
  24. 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...
  25. ncbi request reprint Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation
    Maria E Figueroa
    Weill Cornell Medical College, New York, NY 10065, USA
    Cancer Cell 18:553-67. 2010
    ..Finally, either expression of mutant IDH1/2 or Tet2 depletion impaired hematopoietic differentiation and increased stem/progenitor cell marker expression, suggesting a shared proleukemogenic effect...
  26. 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...
  27. pmc HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans
    Sachie Marubayashi
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    J Clin Invest 120:3578-93. 2010
    ..Importantly, PU-H71 treatment also reduced the mutant allele burden in mice. These data establish what we believe to be a novel therapeutic rationale for HSP90 inhibition in the treatment of JAK2-dependent MPN...
  28. doi request reprint JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation
    Fan Liu
    Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cancer Cell 19:283-94. 2011
    ..These results indicate that phosphorylation of PRMT5 contributes to the mutant JAK2-induced myeloproliferative phenotype...
  29. 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...
  30. pmc Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis
    Raajit Rampal
    Human Oncology and Pathogenesis Program, and Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY Weill Cornell Medical College, New York, NY
    Blood 123:e123-33. 2014
    ....
  31. 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...
  32. 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
    ....
  33. 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...
  34. doi request reprint Sensitivity and resistance of JAK2 inhibitors to myeloproliferative neoplasms
    Neha Bhagwat
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    Int J Hematol 97:695-702. 2013
    ....
  35. pmc A progenitor cell origin of myeloid malignancies
    Hiroshi Haeno
    Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 106:16616-21. 2009
    ..We find mathematical evidence that a progenitor is the most likely cell of origin of JAK2V617F-mutant MPN. These results may also have relevance to other tumor types arising in tissues that are organized as a differentiation hierarchy...
  36. 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
    ....
  37. pmc Isocitrate dehydrogenase mutations in leukemia
    Anna Sophia McKenney
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    J Clin Invest 123:3672-7. 2013
    ..Here we discuss the relevance of IDH mutations to leukemia pathogenesis, therapy, and outcome and how mutations in IDH1 and IDH2 affect the leukemia epigenome, hematopoietic differentiation, and clinical outcome. ..
  38. pmc Role of TET2 and ASXL1 mutations in the pathogenesis of myeloproliferative neoplasms
    Omar Abdel-Wahab
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    Hematol Oncol Clin North Am 26:1053-64. 2012
    ....
  39. 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...
  40. 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
    ....
  41. 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)...
  42. 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...
  43. ncbi 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
    ....
  44. pmc Janus kinase-2 inhibition induces durable tolerance to alloantigen by human dendritic cell-stimulated T cells yet preserves immunity to recall antigen
    Brian C Betts
    Laboratory of Cellular Immunobiology, Immunology Program, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA
    Blood 118:5330-9. 2011
    ....
  45. pmc TET family proteins and their role in stem cell differentiation and transformation
    Luisa Cimmino
    Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA
    Cell Stem Cell 9:193-204. 2011
    ....
  46. 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...
  47. pmc Prognostic relevance of integrated genetic profiling in acute myeloid leukemia
    Jay P Patel
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA
    N Engl J Med 366:1079-89. 2012
    ..The prognostic value of recently identified somatic mutations has not been systematically evaluated in a phase 3 trial of treatment for AML...
  48. 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
    ....
  49. ncbi request reprint Efficacy of Intermittent Combined RAF and MEK Inhibition in a Patient with Concurrent BRAF- and NRAS-Mutant Malignancies
    Omar Abdel-Wahab
    1Human Oncology and Pathogenesis Program, 2Leukemia Service, 3Gastrointestinal Oncology Service, 4Melanoma and Immunotherapeutics Service, Department of Medicine, 5Molecular Diagnostics Service, Department of Pathology, 6Department of Radiology, 7Center for Molecular Oncology, 8Ludwig Center for Cancer Immunotherapy, and 9Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center and 10Weill Cornell Medical College, New York, New York
    Cancer Discov 4:538-45. 2014
    ..These data support testing of intermittent ERK pathway inhibition in the therapy for both RAS-mutant leukemia and BRAF-mutant melanoma. ..
  50. doi request reprint Mining the epigenetic landscape in ALL
    Lindsay M Lafave
    1 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA 2 Gerstner Sloan Kettering Graduate School, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Nat Genet 45:1269-70. 2013
    ....
  51. pmc Macrophages support pathological erythropoiesis in polycythemia vera and β-thalassemia
    Pedro Ramos
    Department of Pediatrics, Division of Hematology Oncology, Weill Cornell Medical College, New York, New York, USA
    Nat Med 19:437-45. 2013
    ..The contribution of macrophages to stress and pathological erythropoiesis, which we have termed stress erythropoiesis macrophage-supporting activity, may have therapeutic implications...
  52. doi request reprint Leveraging cancer genome information in hematologic malignancies
    Raajit Rampal
    Memorial Sloan Kettering Cancer Center, New York, NY, USA
    J Clin Oncol 31:1885-92. 2013
    ..Finally, we discuss general concepts in genetic modeling and the current state-of-the-art technology used in genetic investigation...
  53. 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
    ....
  54. pmc Depletion of L3MBTL1 promotes the erythroid differentiation of human hematopoietic progenitor cells: possible role in 20q- polycythemia vera
    Fabiana Perna
    Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY, USA
    Blood 116:2812-21. 2010
    ..Our data suggest that haploinsufficiency of L3MBTL1 contributes to some (20q-) myeloproliferative neoplasms, especially polycythemia vera, by promoting erythroid differentiation...
  55. pmc Transcriptomic and phospho-proteomic analyzes of erythroblasts expanded in vitro from normal donors and from patients with polycythemia vera
    Todd Hricik
    Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY 10029, USA
    Am J Hematol 88:723-9. 2013
    ..Members of this acquired repertoire may provide important insight into the pathogenesis of aberrant erythropoiesis in myeloproliferative neoplasms such as polycythemia vera...
  56. 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...
  57. pmc Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia
    Julia A Meyer
    New York University Cancer Institute, New York University Langone Medical Center, New York, New York, USA
    Nat Genet 45:290-4. 2013
    ..Clinically, all individuals who harbored NT5C2 mutations relapsed early, within 36 months of initial diagnosis (P = 0.03). These results suggest that mutations in NT5C2 are associated with the outgrowth of drug-resistant clones in ALL...
  58. doi request reprint JAK2 the future: therapeutic strategies for JAK-dependent malignancies
    Lindsay M Lafave
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, NY 10065, USA
    Trends Pharmacol Sci 33:574-82. 2012
    ..These innovative therapies may translate to treatment of other diseases that are dependent on JAK signaling, including B-precursor acute lymphoblastic leukemia (B-ALL)...
  59. ncbi request reprint Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2
    Claudia A Doege
    Department of Pathology, Taub Institute for Aging, Columbia University, New York, New York 10032, USA
    Nature 488:652-5. 2012
    ..These findings suggest that Parp1 and Tet2 contribute to an epigenetic program that directs subsequent transcriptional induction at pluripotency loci during somatic cell reprogramming...
  60. doi request reprint Clinical implications of novel mutations in epigenetic modifiers in AML
    Omar Abdel-Wahab
    Leukemia Service and Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, NY 10065, USA
    Hematol Oncol Clin North Am 25:1119-33. 2011
    ....
  61. doi request reprint Metabolic syndromes and malignant transformation: where the twain shall meet
    Neha Bhagwat
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Sci Transl Med 2:54ps50. 2010
    ..These observations further elucidate the effects of IDH mutations on normal and malignant cells...
  62. pmc A mathematical framework to determine the temporal sequence of somatic genetic events in cancer
    Camille Stephan Otto Attolini
    Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:17604-9. 2010
    ..RESIC represents the first evolutionary mathematical approach to identify the temporal sequence of mutations driving tumorigenesis and may be useful to guide the validation of candidate genes emerging from cancer genome surveys...
  63. 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...
  64. 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...
  65. pmc PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas
    Tatsuya Ozawa
    Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Genes Dev 24:2205-18. 2010
    ..These results suggest the possibility that these PDGFRA mutants behave as oncogenes in this subset of gliomas, and that the prevalence of such rearrangements may have been considerably underestimated...
  66. pmc Finding a needle in a haystack: whole genome sequencing and mutation discovery in murine models
    Raajit K Rampal
    Human Oncology and Pathogenesis Program and Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    J Clin Invest 121:1255-8. 2011
    ..The findings implicate the JAK/STAT pathway in the pathogenesis of APL and illustrate the power of whole genome sequencing to identify novel disease alleles in murine models of disease...
  67. 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...
  68. 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...
  69. pmc JAK Inhibitors and other Novel Agents in Myeloproliferative Neoplasms: Are We Hitting the Target?
    Nicole Kucine
    Human Oncology and Pathogenesis Program and Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, USA
    Ther Adv Hematol 2:203-11. 2011
    ....
  70. doi request reprint New pieces of a puzzle: the current biological picture of MPN
    Maria Kleppe
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Biochim Biophys Acta 1826:415-22. 2012
    ....
  71. pmc Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia
    Panagiotis Ntziachristos
    Howard Hughes Medical Institute and Department of Pathology, New York University School of Medicine, New York, New York, USA
    Nat Med 18:298-301. 2012
    ..These studies suggest a tumor suppressor role for PRC2 in human leukemia and suggest a hitherto unrecognized dynamic interplay between oncogenic NOTCH1 and PRC2 function for the regulation of gene expression and cell transformation...
  72. ncbi request reprint Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
    Ross L Levine
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Cell 7:387-97. 2005
    ..In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase...
  73. 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
    ....
  74. 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...
  75. 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...
  76. 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...
  77. 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
  78. 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...
  79. 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...
  80. pmc JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis
    Linda M Scott
    University of Cambridge, Cambridge, United Kingdom
    N Engl J Med 356:459-68. 2007
    ..However, the molecular basis of these myeloproliferative disorders in patients without the V617F mutation is unclear...
  81. 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...
  82. 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
    ....
  83. 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
    ....
  84. 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...
  85. 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...

Research Grants4

  1. Molecular genetic analysis of tyrosine kinases in myeloproliferative disorders
    Ross Levine; Fiscal Year: 2007
    ..We plan to develop preclinical data that will provide a platform for initiating clinical trials with novel kinase inhibitors. (End 0f Abstract) ..
  2. Molecular Pathogenesis and Therapy of ET and PMF
    Ross L Levine; Fiscal Year: 2010
    ....