Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome

作者：Chae‐Yin Cher, GM Leung, Chun Hang Au, Tsun‐Leung Chan, E S K Ma, Joycelyn Sim, Harinder Gill, Albert K. W. Lie, Raymond Liang, K.F. Wong, Lisa L. P. Siu, Christy Sp Tsui, C.C So, Hera Wong, Sze‐Fai Yip, H K K Lee, H S Y Liu, Jeremy Lau, T H Luk, Chi Kuen Lau, S.-Y. Lin, Yok‐Lam Kwong, Anskar Y.H. Leung, on behalf of the Hong Kong AML Study Group · 发表于：Blood Cancer Journal · 年份：2016 · DOI：10.1038/bcj.2016.51 · 被引用次数：43 · 研究领域：Acute Myeloid Leukemia Research、Myeloproliferative Neoplasms: Diagnosis and Treatment、Epigenetics and DNA Methylation

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.