Determination of complex subclonal structures of hematological malignancies by multiplexed genotyping of blood progenitor colonies

Autor: Nice, Francesca L., Massie, Charlie E., Klampfl, Thorsten, Green, Anthony R. ^*

Publikováno v: In Experimental Hematology January 2018 57:60-64

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Classification and Personalized Prognosis in Myeloproliferative Neoplasms.

Autor: Grinfeld J; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Nangalia J; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Baxter EJ; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Wedge DC; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Angelopoulos N; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Cantrill R; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Godfrey AL; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Papaemmanuil E; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Gundem G; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., MacLean C; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Cook J; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., O'Neil L; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., O'Meara S; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Teague JW; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Butler AP; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Massie CE; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Williams N; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Nice FL; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Andersen CL; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Hasselbalch HC; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Guglielmelli P; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., McMullin MF; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Vannucchi AM; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Harrison CN; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Gerstung M; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Green AR; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.)., Campbell PJ; From the Wellcome-MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research (J.G., C.E.M., F.L.N., A.R.G., P.J.C.), the Department of Haematology, University of Cambridge (J.G., E.J.B., C.M., J.C., C.E.M., F.L.N., A.R.G.), and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust (J.G., E.J.B., A.L.G., C.M., J.C., A.R.G.), Cambridge, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus (J.N., D.C.W., N.A., E.P., G.G., L.O., S.O., J.W.T., A.P.B., N.W., P.J.C.), and the European Molecular Biology Laboratory, European Bioinformatics Institute (R.C., M.G.), Hinxton, Big Data Institute, University of Oxford, Oxford (D.C.W.), the Department of Haematology, Queen's University Belfast, Belfast (M.F.M.), and the Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.) - all in the United Kingdom; the Center for Molecular Oncology and the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York (E.P., G.G.); the Department of Hematology, Zealand University Hospital, Roskilde, and the University of Copenhagen, Copenhagen (C.L.A., H.C.H.); and the Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy (P.G., A.M.V.).

Publikováno v: The New England journal of medicine [N Engl J Med] 2018 Oct 11; Vol. 379 (15), pp. 1416-1430.