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https://hdl.handle.net/2440/133755
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Type: | Journal article |
Title: | Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia |
Author: | Ochi, Y. Yoshida, K. Huang, Y.-J. Kuo, M.-C. Nannya, Y. Sasaki, K. Mitani, K. Hosoya, N. Hiramoto, N. Ishikawa, T. Branford, S. Shanmuganathan, N. Ohyashiki, K. Takahashi, N. Takaku, T. Tsuchiya, S. Kanemura, N. Nakamura, N. Ueda, Y. Yoshihara, S. et al. |
Citation: | Nature Communications, 2021; 12(1):2833-1-2833-13 |
Publisher: | Springer Science and Business Media |
Issue Date: | 2021 |
ISSN: | 2041-1723 2041-1723 |
Statement of Responsibility: | Yotaro Ochi, Kenichi Yoshida, Ying-Jung Huang, Ming-Chung Kuo, Yasuhito Nannya, Ko Sasaki ... et al. |
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. |
Keywords: | Protein Kinase Inhibitors |
Rights: | © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. |
DOI: | 10.1038/s41467-021-23097-w |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1027531 http://purl.org/au-research/grants/nhmrc/1104425 |
Published version: | http://dx.doi.org/10.1038/s41467-021-23097-w |
Appears in Collections: | Medicine publications |
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hdl_133755.pdf | Published version | 1.23 MB | Adobe PDF | View/Open |
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