title: Prevalence and prognostic significance of c-KIT mutations in core binding factor acute myeloid leukemia: a comprehensive large-scale study from a single Chinese center.
abstract: To clarify the prevalence and prognostic significance of c-KIT mutations in patients with core binding factor acute myeloid leukemia (CBF-AML), a total of 351 patients who were categorized as pediatric t(8;21), adult t(8;21), pediatric inv(16), or adult inv(16) were screened at diagnosis for c-KIT mutations in exons 17 and 8 using direct sequencing. A total of 250 patients underwent follow-up. Overall, 36.5% of the patients had a c-KIT mutation. Adult t(8;21) and inv(16) patients had mutations predominantly in exons 17 and 8, respectively. Higher White blood cell (WBC) count, WBC index, and AML1-ETO transcript levels in adult t(8;21) patients were significantly associated with c-KIT mutations and mutations in exon 17 (P≤0.030). c-KIT mutations in adult t(8;21) patients were significantly correlated with a high cumulative incidence of relapse (CIR, P=0.0070) at 2 years and a low 2-year disease-free survival (DFS, P=0.013) and overall survival (OS, P=0.0055). However, no significant difference was revealed in the effect of c-KIT mutations on outcome of adult inv(16) and pediatric t(8;21) patients (all P>0.05). Multivariate analysis revealed that c-KIT mutation is an independent prognostic factor for relapse, DFS, and OS (P≤0.016) in adult t(8;21) AML patients. Therefore, with regard to c-KIT mutation, CBF-AML is a heterogeneous disease. c-KIT mutations have a strong adverse effect on the relapse and survival of adult t(8;21) AML patients.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: Ya-Zhen
authors.initials: YZ
authors.lastname: Qin
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: Hong-Hu
authors.initials: HH
authors.lastname: Zhu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Peking University People's Hospital, Department of Pediatrics, Beijing 100044, China.
authors.forename: Le-Ping
authors.initials: LP
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Liu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: Yue-Yun
authors.initials: YY
authors.lastname: Lai
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Shi
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China; Peking-Tsinghua Center for Life Sciences, Beijing 100871, China. Electronic address: xjhrm@medmail.com.cn.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D007446:Chromosome Inversion; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D015995:Prevalence; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D015996:Survival Rate
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D019009:Proto-Oncogene Proteins c-kit
keywords: Core binding factor acute myeloid leukemia; Prognosis; c-KIT mutations; inv(16); t(8 ;21)