Demethylation and Up-Regulation of an Oncogene after Hypomethylating Therapy.

Autor:	Liu YC; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Kwon J; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Fabiani E; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Xiao Z; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Liu YV; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Follo MY; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Liu J; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Huang H; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Gao C; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Liu J; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Falconi G; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Valentini L; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Gurnari C; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Finelli C; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Cocco L; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Liu JH; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Jones AI; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Yang J; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Yang H; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Thoms JAI; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Unnikrishnan A; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Pimanda JE; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Pan R; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Bassal MA; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Voso MT; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Tenen DG; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia., Chai L; From the Department of Pathology, Brigham and Women's Hospital (Y.-C.L., C. Gao, Jun Liu, J.Y., L. Chai), Harvard Stem Cell Institute, Harvard Medical School (A.I.J., M.A.B., D.G.T.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (R.P.) - all in Boston; the Division of Hematology, Department of Medicine, Taipei Veterans General Hospital (Y.-C.L.), and the Faculty of Medicine and the Program in Molecular Medicine, Institute of Biopharmaceutical Sciences, School of Life Science, National Yang Ming Chiao Tung University (Y.-C.L., J.-H.L.) - both in Taipei, Taiwan; the Cancer Science Institute of Singapore, Singapore (J.K., Y.V.L., H.Y., M.A.B., D.G.T.); the Department of Biomedicine and Prevention, University of Rome Tor Vergata (E.F., G.F., L.V., C. Gurnari, M.T.V.), and UniCamillus-Saint Camillus International University of Health Sciences (E.F.), Rome, and Cellular Signaling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna (M.Y.F., L. Cocco), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' (C.F.), Bologna - all in Italy; the National Clinical Research Center for Blood Diseases and State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (Z.X., Jinqin Liu, H.H.); and the School of Medical Sciences and Lowy Cancer Research Centre (J.A.I.T., J.E.P.) and Prince of Wales Clinical School and Lowy Cancer Research Centre (A.U., J.E.P.), Faculty of Medicine, University of New South Wales, Sydney, and the Department of Hematology, Prince of Wales Hospital, Randwick, NSW (J.E.P.) - both in Australia.
Jazyk:	angličtina
Zdroj:	The New England journal of medicine [N Engl J Med] 2022 May 26; Vol. 386 (21), pp. 1998-2010.
DOI:	10.1056/NEJMoa2119771
Abstrakt:	Background: Although hypomethylating agents are currently used to treat patients with cancer, whether they can also reactivate and up-regulate oncogenes is not well elucidated. Methods: We examined the effect of hypomethylating agents on SALL4 , a known oncogene that plays an important role in myelodysplastic syndrome and other cancers. Paired bone marrow samples that were obtained from two cohorts of patients with myelodysplastic syndrome before and after treatment with a hypomethylating agent were used to explore the relationships among changes in SALL4 expression, treatment response, and clinical outcome. Leukemic cell lines with low or undetectable SALL4 expression were used to study the relationship between SALL4 methylation and expression. A locus-specific demethylation technology, CRISPR-DNMT1-interacting RNA (CRISPR-DiR), was used to identify the CpG island that is critical for SALL4 expression. Results: SALL4 up-regulation after treatment with hypomethylating agents was observed in 10 of 25 patients (40%) in cohort 1 and in 13 of 43 patients (30%) in cohort 2 and was associated with a worse outcome. Using CRISPR-DiR, we discovered that demethylation of a CpG island within the 5' untranslated region was critical for SALL4 expression. In cell lines and patients, we confirmed that treatment with a hypomethylating agent led to demethylation of the same CpG region and up-regulation of SALL4 expression. Conclusions: By combining analysis of patient samples with CRISPR-DiR technology, we found that demethylation and up-regulation of an oncogene after treatment with a hypomethylating agent can indeed occur and should be further studied. (Funded by Associazione Italiana per la Ricerca sul Cancro and others.). (Copyright © 2022 Massachusetts Medical Society.)
Databáze:	MEDLINE
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