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

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 Shanmuganathan, Kazuma Ohyashiki, Naoto Takahashi, Tomoiku Takaku, Shun Tsuchiya, Nobuhiro Kanemura, Nobuhiko Nakamura, Yasunori Ueda, Satoshi Yoshihara, Rabindranath Bera, Yusuke Shiozawa, Lanying Zhao, June Takeda, Yosaku Watatani, Rurika Okuda, Hideki Makishima, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Masashi Sanada, Akifumi Takaori-Kondo, Satoru Miyano, Seishi Ogawa () and Lee-Yung Shih ()
Additional contact information
Yotaro Ochi: 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
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
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
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
Yusuke Shiozawa: Graduate School of Medicine, Kyoto University
Lanying Zhao: Graduate School of Medicine, 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
Lee-Yung Shih: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23097-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23097-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23097-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().