Genetic landscape of pediatric acute myeloid leukemia in Taiwan.
Journal
Scientific reports
Journal Volume
16
Journal Issue
1
ISSN
2045-2322
Date Issued
2026-01-07
Author(s)
Cheng, Zhongshan
Yu, Chih-Hsiang
Chang, Ti-Cheng
Chang, Ya-Hsuan
Lin, Kai-Hsin
Lin, Ze-Shiang
Kuo, Chieh-Wen
Liew, Phooi-Theng
Du, Chia-Jui
Lin, Chien-Yu
Ni, Yu-Ling
Chen, Hsuan-Yu
Lin, Dong-Tsamn
Wu, Gang
Pui, Ching-Hon
Yang, Yung-Li
Abstract
The international consensus classification or the World Health Organization classifications underrepresented driver alterations enriched in pediatric acute myeloid leukemia (AML). To address this, we retrospectively characterized the genomic landscape of 105 pediatric patients with AML of East Asian ancestry using transcriptome and whole-exome sequencing (WES). In addition to the common recurrent fusions such as RUNX1::RUNX1T1 and CBFB::MYH11, we identified rearrangements involving KMT2A, NUP98, GLIS, as well as FLT3 and UBTF tandem duplications. The median somatic mutation rate in AML was 0.97 per megabase, as estimated by WES. Frequently mutated pathways included signaling: 68.6% (72/105), transcription: 37.1% (39/105), epigenetic regulation: 26.7% (28/105), cohesin: 7.6% (8/105), RNA binding: 3.8% (4/105), and protein modification: 5.7% (6/105). When analyzed together, high-risk genetic subtypes including GLISr, UBTF tandem duplications, PICALM::MLLT10, and HOXr were significantly associated with poorer 5 year overall survival (OS) in multivariable analysis (p-value = 0.037). Although FLT3 internal tandem duplications were significantly associated with inferior 5 year OS in univariable analysis, this effect was not significant in multivariable analysis (p-value = 0.382). Patients with RUNX1 mutations had inferior 5 year OS in multivariable analysis (p-value = 0.009). These findings suggest specific genomic alterations that may refine risk stratification and guide future therapeutic protocols in Taiwanese pediatric patients with AML.
Subjects
RUNX1 mutations
Pediatric acute myeloid leukemia
RNA-seq
TPOG
Whole exome sequencing
Type
journal article