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
N1 - Publisher Copyright:
© 2021, The Author(s).
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 -