title: Effect of mutation order on myeloproliferative neoplasms.
abstract: BACKGROUND
  Cancers result from the accumulation of somatic mutations, and their properties are thought to reflect the sum of these mutations. However, little is known about the effect of the order in which mutations are acquired.
  
  
  METHODS
  We determined mutation order in patients with myeloproliferative neoplasms by genotyping hematopoietic colonies or by means of next-generation sequencing. Stem cells and progenitor cells were isolated to study the effect of mutation order on mature and immature hematopoietic cells.
  
  
  RESULTS
  The age at which a patient presented with a myeloproliferative neoplasm, acquisition of JAK2 V617F homozygosity, and the balance of immature progenitors were all influenced by mutation order. As compared with patients in whom the TET2 mutation was acquired first (hereafter referred to as "TET2-first patients"), patients in whom the Janus kinase 2 (JAK2) mutation was acquired first ("JAK2-first patients") had a greater likelihood of presenting with polycythemia vera than with essential thrombocythemia, an increased risk of thrombosis, and an increased sensitivity of JAK2-mutant progenitors to ruxolitinib in vitro. Mutation order influenced the proliferative response to JAK2 V617F and the capacity of double-mutant hematopoietic cells and progenitor cells to generate colony-forming cells. Moreover, the hematopoietic stem-and-progenitor-cell compartment was dominated by TET2 single-mutant cells in TET2-first patients but by JAK2-TET2 double-mutant cells in JAK2-first patients. Prior mutation of TET2 altered the transcriptional consequences of JAK2 V617F in a cell-intrinsic manner and prevented JAK2 V617F from up-regulating genes associated with proliferation.
  
  
  CONCLUSIONS
  The order in which JAK2 and TET2 mutations were acquired influenced clinical features, the response to targeted therapy, the biology of stem and progenitor cells, and clonal evolution in patients with myeloproliferative neoplasms. (Funded by Leukemia and Lymphoma Research and others.).
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Christina A
authors: CA
authors: Ortmann
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: David G
authors: DG
authors: Kent
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Jyoti
authors: J
authors: Nangalia
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Yvonne
authors: Y
authors: Silber
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: David C
authors: DC
authors: Wedge
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Jacob
authors: J
authors: Grinfeld
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: E Joanna
authors: EJ
authors: Baxter
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Charles E
authors: CE
authors: Massie
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Elli
authors: E
authors: Papaemmanuil
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Suraj
authors: S
authors: Menon
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Anna L
authors: AL
authors: Godfrey
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Danai
authors: D
authors: Dimitropoulou
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Paola
authors: P
authors: Guglielmelli
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Beatriz
authors: B
authors: Bellosillo
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Carles
authors: C
authors: Besses
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Konstanze
authors: K
authors: Döhner
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Claire N
authors: CN
authors: Harrison
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: George S
authors: GS
authors: Vassiliou
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Alessandro
authors: A
authors: Vannucchi
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Peter J
authors: PJ
authors: Campbell
authors: Cambridge Institute for Medical Research and Wellcome Trust-Medical Research Council Stem Cell Institute (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., A.R.G.) and Department of Hematology (C.A.O., D.G.K., J.N., Y.S., J.G., E.J.B., C.E.M., A.L.G., D.D., G.S.V., P.J.C., A.R.G.), University of Cambridge, Department of Haematology, Addenbrooke's Hospital (C.A.O., J.N., J.G., E.J.B., A.L.G., G.S.V., P.J.C., A.R.G.), Wellcome Trust Sanger Institute (D.C.W., E.P., G.S.V., P.J.C.), and Cancer Research U.K. Cambridge Institute, Li Ka Shing Centre (S.M.), Cambridge, and Guy's and St. Thomas' National Health Service Foundation Trust, Guy's Hospital, London (C.N.H.) - all in the United Kingdom; Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy (P.G., A.V.); Departments of Pathology (B.B.) and Hematology (C.B.), Hospital del Mar, Barcelona; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany (K.D.).
authors: Anthony R
authors: AR
authors: Green
mesh_terms: D017668:Age of Onset; D049109:Cell Proliferation / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006720:Homozygote; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics*; D011087:Polycythemia Vera / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics; D013927:Thrombosis / Q000235:genetics; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2