Cargando…
Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia
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 B...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121838/ https://www.ncbi.nlm.nih.gov/pubmed/33990592 http://dx.doi.org/10.1038/s41467-021-23097-w |
| _version_ | 1783692462668120064 |
|---|---|
| author | Ochi, Yotaro Yoshida, Kenichi Huang, Ying-Jung Kuo, Ming-Chung Nannya, Yasuhito Sasaki, Ko Mitani, Kinuko Hosoya, Noriko Hiramoto, Nobuhiro Ishikawa, Takayuki Branford, Susan Shanmuganathan, Naranie Ohyashiki, Kazuma Takahashi, Naoto Takaku, Tomoiku Tsuchiya, Shun Kanemura, Nobuhiro Nakamura, Nobuhiko Ueda, Yasunori Yoshihara, Satoshi Bera, Rabindranath Shiozawa, Yusuke Zhao, Lanying Takeda, June Watatani, Yosaku Okuda, Rurika Makishima, Hideki Shiraishi, Yuichi Chiba, Kenichi Tanaka, Hiroko Sanada, Masashi Takaori-Kondo, Akifumi Miyano, Satoru Ogawa, Seishi Shih, Lee-Yung |
| author_facet | Ochi, Yotaro Yoshida, Kenichi Huang, Ying-Jung Kuo, Ming-Chung Nannya, Yasuhito Sasaki, Ko Mitani, Kinuko Hosoya, Noriko Hiramoto, Nobuhiro Ishikawa, Takayuki Branford, Susan Shanmuganathan, Naranie Ohyashiki, Kazuma Takahashi, Naoto Takaku, Tomoiku Tsuchiya, Shun Kanemura, Nobuhiro Nakamura, Nobuhiko Ueda, Yasunori Yoshihara, Satoshi Bera, Rabindranath Shiozawa, Yusuke Zhao, Lanying Takeda, June Watatani, Yosaku Okuda, Rurika Makishima, Hideki Shiraishi, Yuichi Chiba, Kenichi Tanaka, Hiroko Sanada, Masashi Takaori-Kondo, Akifumi Miyano, Satoru Ogawa, Seishi Shih, Lee-Yung |
| author_sort | Ochi, Yotaro |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-8121838 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-81218382021-05-18 Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia Ochi, Yotaro Yoshida, Kenichi Huang, Ying-Jung Kuo, Ming-Chung Nannya, Yasuhito Sasaki, Ko Mitani, Kinuko Hosoya, Noriko Hiramoto, Nobuhiro Ishikawa, Takayuki Branford, Susan Shanmuganathan, Naranie Ohyashiki, Kazuma Takahashi, Naoto Takaku, Tomoiku Tsuchiya, Shun Kanemura, Nobuhiro Nakamura, Nobuhiko Ueda, Yasunori Yoshihara, Satoshi Bera, Rabindranath Shiozawa, Yusuke Zhao, Lanying Takeda, June Watatani, Yosaku Okuda, Rurika Makishima, Hideki Shiraishi, Yuichi Chiba, Kenichi Tanaka, Hiroko Sanada, Masashi Takaori-Kondo, Akifumi Miyano, Satoru Ogawa, Seishi Shih, Lee-Yung Nat Commun Article 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. Nature Publishing Group UK 2021-05-14 /pmc/articles/PMC8121838/ /pubmed/33990592 http://dx.doi.org/10.1038/s41467-021-23097-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Ochi, Yotaro Yoshida, Kenichi Huang, Ying-Jung Kuo, Ming-Chung Nannya, Yasuhito Sasaki, Ko Mitani, Kinuko Hosoya, Noriko Hiramoto, Nobuhiro Ishikawa, Takayuki Branford, Susan Shanmuganathan, Naranie Ohyashiki, Kazuma Takahashi, Naoto Takaku, Tomoiku Tsuchiya, Shun Kanemura, Nobuhiro Nakamura, Nobuhiko Ueda, Yasunori Yoshihara, Satoshi Bera, Rabindranath Shiozawa, Yusuke Zhao, Lanying Takeda, June Watatani, Yosaku Okuda, Rurika Makishima, Hideki Shiraishi, Yuichi Chiba, Kenichi Tanaka, Hiroko Sanada, Masashi Takaori-Kondo, Akifumi Miyano, Satoru Ogawa, Seishi Shih, Lee-Yung Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia |
| title | Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia |
| title_full | Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia |
| title_fullStr | Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia |
| title_full_unstemmed | Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia |
| title_short | Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia |
| title_sort | clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121838/ https://www.ncbi.nlm.nih.gov/pubmed/33990592 http://dx.doi.org/10.1038/s41467-021-23097-w |
| work_keys_str_mv | AT ochiyotaro clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT yoshidakenichi clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT huangyingjung clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT kuomingchung clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT nannyayasuhito clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT sasakiko clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT mitanikinuko clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT hosoyanoriko clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT hiramotonobuhiro clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT ishikawatakayuki clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT branfordsusan clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT shanmuganathannaranie clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT ohyashikikazuma clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT takahashinaoto clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT takakutomoiku clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT tsuchiyashun clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT kanemuranobuhiro clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT nakamuranobuhiko clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT uedayasunori clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT yoshiharasatoshi clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT berarabindranath clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT shiozawayusuke clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT zhaolanying clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT takedajune clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT watataniyosaku clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT okudarurika clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT makishimahideki clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT shiraishiyuichi clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT chibakenichi clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT tanakahiroko clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT sanadamasashi clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT takaorikondoakifumi clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT miyanosatoru clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT ogawaseishi clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia AT shihleeyung clonalevolutionandclinicalimplicationsofgeneticabnormalitiesinblastictransformationofchronicmyeloidleukaemia |