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Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

Author

Listed:
  • Yotaro Ochi

    (Graduate School of Medicine, Kyoto University
    Graduate School of Medicine, Kyoto University)

  • Kenichi Yoshida

    (Graduate School of Medicine, Kyoto University)

  • Ying-Jung Huang

    (Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou)

  • Ming-Chung Kuo

    (Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou
    Chang Gung University)

  • Yasuhito Nannya

    (Graduate School of Medicine, Kyoto University)

  • Ko Sasaki

    (Dokkyo Medical University)

  • Kinuko Mitani

    (Dokkyo Medical University)

  • Noriko Hosoya

    (Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo
    Graduate School of Medicine, The University of Tokyo)

  • Nobuhiro Hiramoto

    (Kobe City Medical Center General Hospital)

  • Takayuki Ishikawa

    (Kobe City Medical Center General Hospital)

  • Susan Branford

    (Centre for Cancer Biology, SA Pathology)

  • Naranie Shanmuganathan

    (Centre for Cancer Biology, SA Pathology
    Royal Adelaide Hospital and SA Pathology)

  • Kazuma Ohyashiki

    (Tokyo Medical University)

  • Naoto Takahashi

    (Nephrology, and Rheumatology, Akita University Graduate School of Medicine)

  • Tomoiku Takaku

    (Juntendo University School of Medicine)

  • Shun Tsuchiya

    (Juntendo University School of Medicine)

  • Nobuhiro Kanemura

    (Gifu University Hospital)

  • Nobuhiko Nakamura

    (Gifu University Hospital)

  • Yasunori Ueda

    (Kurashiki Central Hospital)

  • Satoshi Yoshihara

    (Hyogo College of Medicine Hospital)

  • Rabindranath Bera

    (Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou
    Chang Gung University)

  • Yusuke Shiozawa

    (Graduate School of Medicine, Kyoto University)

  • Lanying Zhao

    (Graduate School of Medicine, Kyoto University
    Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University)

  • June Takeda

    (Graduate School of Medicine, Kyoto University)

  • Yosaku Watatani

    (Graduate School of Medicine, Kyoto University)

  • Rurika Okuda

    (Graduate School of Medicine, Kyoto University)

  • Hideki Makishima

    (Graduate School of Medicine, Kyoto University)

  • Yuichi Shiraishi

    (Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo)

  • Kenichi Chiba

    (Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo)

  • Hiroko Tanaka

    (Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo)

  • Masashi Sanada

    (Clinical Research Center, National Hospital Organization Nagoya Medical Center)

  • Akifumi Takaori-Kondo

    (Graduate School of Medicine, Kyoto University)

  • Satoru Miyano

    (Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo)

  • Seishi Ogawa

    (Graduate School of Medicine, Kyoto University
    Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University
    Centre for Haematology and Regenerative Medicine, Karolinska Institute)

  • Lee-Yung Shih

    (Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou
    Chang Gung University)

Abstract

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML.

Suggested Citation

  • Yotaro Ochi & Kenichi Yoshida & Ying-Jung Huang & Ming-Chung Kuo & Yasuhito Nannya & Ko Sasaki & Kinuko Mitani & Noriko Hosoya & Nobuhiro Hiramoto & Takayuki Ishikawa & Susan Branford & Naranie Shanmu, 2021. "Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23097-w
    DOI: 10.1038/s41467-021-23097-w
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