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
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.