Research Topics
Genomes and Genes | Ross L LevineSummaryAffiliation: Harvard University Country: USA Publications
| Collaborators
|
Detail Information
Publications
LS104, a non-ATP-competitive small-molecule inhibitor of JAK2, is potently inducing apoptosis in JAK2V617F-positive cellsDaniel 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...- JAK2 and MPL mutations in myeloproliferative neoplasmsPriya 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... 
JAK-2 mutations and their relevance to myeloproliferative diseaseRoss 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...- Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia veraGerlinde 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.... - Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate allelesStefan Fröhling
Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Cancer Cell 12:501-13. 2007.... 
MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasiaYana Pikman
Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
PLoS Med 3:e270. 2006....- FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemiaBenjamin 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... - Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromesRafael 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... - JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation modelThomas 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... - Concurrent MPL515 and JAK2V617F mutations in myelofibrosis: chronology of clonal emergence and changes in mutant allele burden over timeTerra 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... - The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse modelThomas 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.... - Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemiasOmar 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... - Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcomeSu 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... - Clinical effect of point mutations in myelodysplastic syndromesRafael 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... - MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patientsAnimesh 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... - Role of JAK2 in the pathogenesis and therapy of myeloproliferative disordersRoss 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.... - IDH1 mutations disrupt blood, brain, and barriersAlan 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... - Metabolism and the leukemic stem cellOmar 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)... - Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignanciesOmar 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... - Advances in the molecular characterization of Philadelphia-negative chronic myeloproliferative disordersYana 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... - Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant modelGerlinde Wernig
Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Blood 107:4274-81. 2006.... - The role of mutations in epigenetic regulators in myeloid malignanciesAlan 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.... - Translocation t(11;17) in de novo myelodysplastic syndrome not associated with acute myeloid or acute promyelocytic leukemiaMuhamed Baljevic
Department of Medicine, New York Presbyterian Hospital Weill Cornell Medical Center, New York, NY 10065, USA
Acta Haematol 129:48-54. 2013.... - Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathwaysMarit 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... - Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibitionOliver 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... - 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 hematopoiesisRoss 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... - Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domainJeffrey 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... - The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaratePatrick 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.... - Janus kinase mutationsRoss 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... - Mechanisms of mutations in myeloproliferative neoplasmsRoss 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... - 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... - Acute myeloid leukemia with translocation t(8;16) presents with features which mimic acute promyelocytic leukemia and is associated with poor prognosisAdi 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... - Molecular biology of myelodysplastic syndromesAlan 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... - A mathematical methodology for determining the temporal order of pathway alterations arising during gliomagenesisYu 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.... - The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemiaRoss 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... - Genetics of myeloid malignancies: pathogenetic and clinical implicationsStefan 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... - The JAK2V617F mutation is acquired secondary to the predisposing alteration in familial polycythaemia veraHolger Cario
Br J Haematol 130:800-1. 2005 - The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromesDavid 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... - Rare occurrence of the JAK2 V617F mutation in AML subtypes M5, M6, and M7Stefan Fröhling
Blood 107:1242-3. 2006 - Atrial fibrillation is associated with severe acute ischemic strokeDouglas 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... - Highly sensitive method for genomewide detection of allelic composition in nonpaired, primary tumor specimens by use of affymetrix single-nucleotide-polymorphism genotyping microarraysGo 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... - Myeloproliferative disordersRoss 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...