Genomic Determinants of Induction Failure and Persistent Prognostic Risk of FLT3-ITD in Pediatric Acute Myeloid Leukemia
- 1Department of Hematology and Oncology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents’ Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Intelligent Application of Big Data in Pediatrics Engineering Research Center of Chongqing Education Commission of China, Chongqing 400014, China
Abstract
Background: Induction failure (IF) after standard induction chemotherapy is associated with poor outcomes in pediatric acute myeloid leukemia (pAML); however, whether established molecular markers such as FLT3-ITD retain prognostic significance across induction response states remains incompletely understood. We characterized the genomic landscape of IF and evaluated the prognostic significance of FLT3-ITD according to induction response. Methods: This multi-cohort study integrated a TARGET discovery cohort (n = 1979) and an independent cohort from the Children’s Hospital of Chongqing Medical University (CHCMU; n = 98). Clinical characteristics, somatic mutations, fusion profiles, and gene–gene interaction patterns were compared between patients with and without IF. Multivariable logistic regression identified genomic factors associated with IF, and survival analyses evaluated the prognostic impact of FLT3-ITD according to induction response. Results: IF was associated with inferior OS (overall survival) (pooled HR = 3.24, 95% CI: 2.66–3.95). FLT3 mutations were consistently enriched in IF patients, whereas KIT mutations and favorable core-binding factor fusions were more frequent among non-IF patients. NUP98-NSD1 fusion was strongly enriched in IF patients in the TARGET cohort. Gene interaction analyses revealed reduced recurrent co-mutation patterns among IF patients. FLT3 mutation independently and reproducibly associated with IF. Among patients achieving induction remission, FLT3-ITD remained associated with inferior OS (HR = 1.34, 95% CI: 1.06–1.69, p = 0.014), whereas no statistically significant additional prognostic effect was detected among patients with IF. Conclusions: This study characterizes the genomic landscape of IF in pAML and identifies FLT3 mutation as a reproducible marker of induction resistance. Achieving induction remission does not eliminate the adverse prognostic significance of FLT3-ITD, supporting the integration of molecular risk and treatment response in subsequent risk stratification.
Related
- Determinants and Prognostic Value of Persistent Congestion Assessed by Venous Excess Ultrasound Score in Acute Heart Failure
- Clinical outcomes and prognostic factors in pediatric acute myeloid leukemia with monocytic differentiation: a single-center cohort study from Egypt
- Systemic Mastocytosis With Associated Acute Myeloid Leukemia Identified After Induction Therapy: A Case Report and Literature Review
- The Utility of Computed Tomography of the Chest at the Time of Induction Chemotherapy in Patients with Acute Leukemia
- Response to Venetoclax and Azacitidine in Induction-Refractory Adult Acute Myeloid Leukemia with UBTF Tandem Duplication and Associated Aberrant Splicing: A Case Report
BibTeX
@article{liu2026genomic,
title = {{Genomic Determinants of Induction Failure and Persistent Prognostic Risk of FLT3-ITD in Pediatric Acute Myeloid Leukemia}},
author = {Rongqiu Liu and Yinghui Cui and Lan Huang and Xianmin Guan and Yali Shen and Ying Dou and Xianhao Wen and Yuxia Guo and Haiyan Liu and Xinyuan Yao and Yan Xiang and Xing Zeng and Qiao Liu and Jie Yu},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203280},
url = {https://www.mdpi.com/2072-6694/18/20/3280},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Genomic Determinants of Induction Failure and Persistent Prognostic Risk of FLT3-ITD in Pediatric Acute Myeloid Leukemia
AU - Rongqiu Liu
AU - Yinghui Cui
AU - Lan Huang
AU - Xianmin Guan
AU - Yali Shen
AU - Ying Dou
AU - Xianhao Wen
AU - Yuxia Guo
AU - Haiyan Liu
AU - Xinyuan Yao
AU - Yan Xiang
AU - Xing Zeng
AU - Qiao Liu
AU - Jie Yu
PY - 2026
DA - 2026/10/12
JO - Cancers
DO - 10.3390/cancers18203280
UR - https://www.mdpi.com/2072-6694/18/20/3280
AB - Background: Induction failure (IF) after standard induction chemotherapy is associated with poor outcomes in pediatric acute myeloid leukemia (pAML); however, whether established molecular markers such as FLT3-ITD retain prognostic significance across induction response states remains incompletely understood. We characterized the genomic landscape of IF and evaluated the prognostic significance of FLT3-ITD according to induction response. Methods: This multi-cohort study integrated a TARGET discovery cohort (n = 1979) and an independent cohort from the Children’s Hospital of Chongqing Medical University (CHCMU; n = 98). Clinical characteristics, somatic mutations, fusion profiles, and gene–gene interaction patterns were compared between patients with and without IF. Multivariable logistic regression identified genomic factors associated with IF, and survival analyses evaluated the prognostic impact of FLT3-ITD according to induction response. Results: IF was associated with inferior OS (overall survival) (pooled HR = 3.24, 95% CI: 2.66–3.95). FLT3 mutations were consistently enriched in IF patients, whereas KIT mutations and favorable core-binding factor fusions were more frequent among non-IF patients. NUP98-NSD1 fusion was strongly enriched in IF patients in the TARGET cohort. Gene interaction analyses revealed reduced recurrent co-mutation patterns among IF patients. FLT3 mutation independently and reproducibly associated with IF. Among patients achieving induction remission, FLT3-ITD remained associated with inferior OS (HR = 1.34, 95% CI: 1.06–1.69, p = 0.014), whereas no statistically significant additional prognostic effect was detected among patients with IF. Conclusions: This study characterizes the genomic landscape of IF in pAML and identifies FLT3 mutation as a reproducible marker of induction resistance. Achieving induction remission does not eliminate the adverse prognostic significance of FLT3-ITD, supporting the integration of molecular risk and treatment response in subsequent risk stratification.
SN - 2072-6694
ER -