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; Lee Yung Shih

doi:10.1038/s41467-021-23097-w

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 YoshiharaRabindranath 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^*, Lee Yung Shih^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Journal Article › peer-review

49 Scopus citations

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.

Original language	English
Article number	2833
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-23097-w
State	Published - 01 12 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Access to Document

10.1038/s41467-021-23097-w

Cite this

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., ... Shih, L. Y. (2021). Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia. Nature Communications, 12(1), Article 2833. https://doi.org/10.1038/s41467-021-23097-w

@article{842c58454bcf4631b4173d84b09a981b,

title = "Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia",

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.",

author = "Yotaro Ochi and Kenichi Yoshida and Huang, {Ying Jung} and Kuo, {Ming Chung} and Yasuhito Nannya and Ko Sasaki and Kinuko Mitani and Noriko Hosoya and Nobuhiro Hiramoto and Takayuki Ishikawa and Susan Branford and Naranie Shanmuganathan and Kazuma Ohyashiki and Naoto Takahashi and Tomoiku Takaku and Shun Tsuchiya and Nobuhiro Kanemura and Nobuhiko Nakamura and Yasunori Ueda and Satoshi Yoshihara and Rabindranath Bera and Yusuke Shiozawa and Lanying Zhao and June Takeda and Yosaku Watatani and Rurika Okuda and Hideki Makishima and Yuichi Shiraishi and Kenichi Chiba and Hiroko Tanaka and Masashi Sanada and Akifumi Takaori-Kondo and Satoru Miyano and Seishi Ogawa and Shih, {Lee Yung}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-021-23097-w",

language = "英语",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Ochi, Y, Yoshida, K, Huang, YJ, Kuo, MC, 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, Bera, R, Shiozawa, Y, Zhao, L, Takeda, J, Watatani, Y, Okuda, R, Makishima, H, Shiraishi, Y, Chiba, K, Tanaka, H, Sanada, M, Takaori-Kondo, A, Miyano, S, Ogawa, S & Shih, LY 2021, 'Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia', Nature Communications, vol. 12, no. 1, 2833. https://doi.org/10.1038/s41467-021-23097-w

TY - JOUR

T1 - Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

AU - Ochi, Yotaro

AU - Yoshida, Kenichi

AU - Huang, Ying Jung

AU - Kuo, Ming Chung

AU - Nannya, Yasuhito

AU - Sasaki, Ko

AU - Mitani, Kinuko

AU - Hosoya, Noriko

AU - Hiramoto, Nobuhiro

AU - Ishikawa, Takayuki

AU - Branford, Susan

AU - Shanmuganathan, Naranie

AU - Ohyashiki, Kazuma

AU - Takahashi, Naoto

AU - Takaku, Tomoiku

AU - Tsuchiya, Shun

AU - Kanemura, Nobuhiro

AU - Nakamura, Nobuhiko

AU - Ueda, Yasunori

AU - Yoshihara, Satoshi

AU - Bera, Rabindranath

AU - Shiozawa, Yusuke

AU - Zhao, Lanying

AU - Takeda, June

AU - Watatani, Yosaku

AU - Okuda, Rurika

AU - Makishima, Hideki

AU - Shiraishi, Yuichi

AU - Chiba, Kenichi

AU - Tanaka, Hiroko

AU - Sanada, Masashi

AU - Takaori-Kondo, Akifumi

AU - Miyano, Satoru

AU - Ogawa, Seishi

AU - Shih, Lee Yung

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85105958378&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-23097-w

DO - 10.1038/s41467-021-23097-w

M3 - 文章

C2 - 33990592

AN - SCOPUS:85105958378

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2833

ER -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this