Characterization of mutational pattern of patients with core-binding factor acute myeloid leukemia.
10.3760/cma.j.issn.1003-9406.2019.07.001
- Author:
Jinyuan HE
1
;
Hongying CHAO
;
Min ZHOU
;
Xuzhang LU
;
Tao CHEN
;
Jianhe YANG
;
Naike JIANG
;
Ri ZHANG
Author Information
1. The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, China. chaohy2006@126.com.
- Publication Type:Journal Article
- MeSH:
Core Binding Factors;
genetics;
DNA Mutational Analysis;
Humans;
Leukemia, Myeloid, Acute;
genetics;
Mutation;
Prognosis
- From:
Chinese Journal of Medical Genetics
2019;36(7):657-661
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To characterize the mutational profile of patients with core-binding factor acute myeloid leukemia (CBF-AML).
METHODS:A total of 81 acute myeloid leukemia patients were recruited, which included 36 cases of CBF-AML and 45 cases of cytogenetically normal acute myeloid leukemia (CN-AML) . Mutations of FLT3-ITD, FLT3-TKD, NPM1, c-KIT, NRAS, KRAS, TET2, IDH1/2, RUNX1, DNMT3A, GATA2, ASjXL1, TP53, PTPN11, JAK2V617F, SETBP1 and CEBPA genes were simultaneously detected by DNA-based PCR and Sanger sequencing.
RESULTS:Over all, mutations were detected in 68 patients (83.9%), with the most common ones including double CEBPA mutations (n=17), followed by NPM1 (n=15), c-KIT (n=11), NRAS (n=10), TET2 (n=9), FLT3-TKD (n=9), FLT3-ITD (n=8), IDH1 (n=7), RUNX1 (n=7), KRAS (n=7), DNMT3A (n=6), IDH2 (n=4), and GATA2 (n=4) mutations. AML1-ETO and CBFβ-MYH11 fusions were present in 21 and 15 patients, respectively. Coexistence of ≥2 mutations was more common in CN-AML comparing with CBF-AML. The mutation rate of NPM1, FLT3-ITD, DNMT3A, IDH1 and CEBPA double mutations were higher in patients with CN-AML. NRAS, c-KIT and KRAS mutations were identified more frequently in patients with CBF-AML (P<0.05). Based on the function, aberration of genes involved in DNA methylation, NPM1 proteins and transcription predominated in CN-AML, while tyrosine kinase receptor signaling and RAS pathways have predominated in CBF-AML.
CONCLUSION:The genomic landscape of CBF-AML patients has differed from that of CN-AML patients. Synergy of fusion genes with particular mutations may impact the clinical phenotype and prognosis of patients.
