Prognostic value of KIT and other clonal genetic mutations in core-binding factor acute myeloid leukemia
10.3760/cma.j.issn.0253-2727.2021.08.006
- VernacularTitle:KIT及其他克隆性基因突变对核心结合因子相关急性髓系白血病的预后价值
- Author:
Tianmei WU
1
;
Shengli XUE
;
Zheng LI
;
Jingqiu YU
;
Jun WANG
;
Binru WANG
;
Chaoling WAN
;
Xiangdong SHEN
;
Qiaocheng QIU
;
Xiebing BAO
;
Depei WU
Author Information
1. 苏州大学附属第一医院、江苏省血液研究所、国家血液系统疾病临床医学研究中心、国家卫生健康委员会血栓与止血重点实验室，苏州 215006
- Keywords:
Core binding factors;
Leukemia, myeloid, acute;
Genetic mutations;
Gene, KIT
- From:
Chinese Journal of Hematology
2021;42(8):646-653
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the prognostic significance of clonal gene mutations using next-generation sequencing in patients with core-binding factor acute myeloid leukemia (CBF-AML) who achieved first complete remission after induction chemotherapy.Methods:The study, which was conducted from July 2011 to August 2017 in First Affiliated Hospital of Soochow University, comprised 195 newly diagnosed patients with CBF-AML, including 190 patients who achieved first complete remission after induction chemotherapy. The cohort included 134 patients with RUNX1-RUNXIT1 + AML and 56 patients with CBFβ-MYH11 + AML. The cohort age ranged from 15 to 64 years, with a median follow-up of 43.6 months. Overall survival (OS) and disease-free survival (DFS) were assessed by the log-rank test, and the Cox proportional hazards regression model was used to determine the effects of clinical factors and genetic mutations on prognosis. Results:The most common genetic mutations were in KIT (47.6% ) , followed by NRAS (20.0% ) , FLT3 (18.4% ) , ASXL2 (14.3% ) , KRAS (10.7% ) , and ASXL1 (9.7% ) . The most common mutations involved genes affecting tyrosine kinase signaling (76.4% ) , followed by chromatin modifiers (29.7% ) . Among the patients receiving intensive consolidation therapy, the OS tended to be better in patients with CBFβ-MYH11 + AML than in those with RUNX1-RUNXIT1 + AML ( P=0.062) . Gene mutations related to chromatin modification, which were detected only in patients with RUNX1-RUNXIT1 + AML, did not affect DFS ( P=0.557) . The patients with mutations in genes regulating chromatin conformation who received allo-hematopoietic stem cell transplantation (allo-HSCT) achieved the best prognosis. Multivariate analysis identified KIT exon 17 mutations as an independent predictor of inferior DFS in patients with RUNX1-RUNXIT1 + AML ( P<0.001) , and allo-HSCT significantly prolonged DFS in these patients ( P=0.010) . Conclusions:KIT exon 17 mutations might indicate poor prognosis in patients with RUNX1-RUNXIT1 + AML. Allo-HSCT may improve prognosis in these patients, whereas allo-HSCT might also improve prognosis in patients with mutations in genes related to chromatin modifications.
