Related Experiment Video
Updated: May 6, 2026
Selecting Multiple Biomarker Subsets with Similarly Effective Binary Classification Performances
Published on: October 11, 2018
Prospective Evaluation of KIT Mutations and Long-Term Outcomes in Pediatric Core Binding Factor Acute Myeloid
Bei Hou1, Feifei Yang1, Ruidong Zhang1
1Department of Leukemia,Hematology Center, National Key Discipline of Pediatric Hematology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Insights
KIT mutations impact outcomes in pediatric core binding factor acute myeloid leukemia (CBF-AML). Identifying KIT exon 17 mutations improves risk stratification and guides treatment for better survival in high-risk patients.
Area of Science:
- Pediatric Hematology Oncology
- Molecular Diagnostics
- Cancer Genomics
Background:
- Core binding factor acute myeloid leukemia (CBF-AML) incidence in children varies (19%-44.3%).
- The prognostic significance of KIT mutations in pediatric CBF-AML is debated.
- Current risk stratification may not fully capture outcomes for all pediatric CBF-AML patients.
Purpose of the Study:
- To determine if including KIT mutation status in risk stratification improves long-term outcomes for pediatric CBF-AML.
- To evaluate the prognostic role of KIT mutations across different genetic subgroups of pediatric CBF-AML.
- To assess the impact of KIT exon 17 mutational status on overall survival (OS) and event-free survival (EFS).
Main Methods:
- Retrospective analysis of 114 pediatric CBF-AML patients from BCH-AML 2005 and CCLG-AML 2015 protocols.
- Sanger sequencing to identify KIT mutations.
- Statistical evaluation of clinical features, genetic subgroups, and outcomes in relation to KIT mutation status.
Main Results:
- KIT mutations were found in 25.4% of pediatric CBF-AML patients, with similar rates in RUNX1::RUNX1T1 and CBFβ::MYH11 subgroups.
- Patients with KIT mutations had higher leukemia burdens (increased blasts, WBC).
- KIT exon 17 mutations (KITmut17+) were associated with significantly lower OS and EFS compared to KIT exon 8 mutations (KITmut8+) and wild-type (KITwt).
Conclusions:
- Prospective evaluation of KIT mutations is crucial for pediatric CBF-AML risk stratification.
- KIT exon 17 status is an independent prognostic factor for OS and EFS in CBF-AML, especially in RUNX1::RUNX1T1 patients.
- High-risk chemotherapy and stem cell transplantation can improve survival for pediatric RUNX1::RUNX1T1 patients with KIT mutations.
Abstract:
The overall incidence of core binding factor acute myeloid leukemia (CBF-AML) in pediatric patients has been reported to be 19%-44.3%. However, the prognostic role of KIT mutations in pediatric CBF-AML remains controversial. This study aimed to investigate whether incorporating KIT mutation status into risk stratification improves long-term outcomes. A total of 114 pediatric CBF-AML patients treated under BCH-AML 2005 protocol and CCLG-AML 2015 protocol were enrolled. KIT mutations were identified using Sanger sequencing, classified as high-risk in CCLG-AML 2015. Relationships between clinical and biological features, outcomes and KIT mutations were evaluated across genetic subgroups. KIT mutations were identified in 25.4% pediatric CBF-AML, with comparable mutation rates in RUNX1::RUNX1T1 and CBFβ::MYH11 subgroups. Patients with KIT mutations showed higher leukemia burdens, including increased bone marrow blasts and white blood cell (WBC) indices. RUNX1::RUNX1T1 subgroup showed poorer 5-year OS than CBFβ::MYH11. Patients with KITmut17+ exhibited significantly lower OS, EFS compared to those with KITmut8+ and KITwt. Notably, RUNX1::RUNX1T1+KITmut17+ patients exhibited significantly worse OS among genetic subgroups but achieved improved OS under CCLG-AML 2015. KIT exon 17 mutational status and treatment protocol was identified as independent prognostic factors for OS and EFS in CBF-AML and RUNX1::RUNX1T1-AML. Our study found that prospective evaluation of KIT mutations is crucial in pediatric CBF-AML, particularly in RUNX1::RUNX1T1 patients, where the survival can be significantly improved by high-risk chemotherapy and hematopoietic stem cell transplantation.
