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<p>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 <i>RUNX1::RUNX1T1</i> and <i>CBFB::MYH11</i>, we identified rearrangements involving <i>KMT2A</i>, <i>NUP98</i>, <i>GLIS</i>, as well as <i>FLT3</i> and <i>UBTF</i> 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 <i>GLISr</i>, <i>UBTF</i> tandem duplications, <i>PICALM::MLLT10</i>, and <i>HOXr</i> were significantly associated with poorer 5&#xa0;year overall survival (OS) in multivariable analysis (<i>p</i>-value = 0.037). Although <i>FLT3</i> internal tandem duplications were significantly associated with inferior 5&#xa0;year OS in univariable analysis, this effect was not significant in multivariable analysis (<i>p</i>-value = 0.382). Patients with <i>RUNX1</i> mutations had inferior 5&#xa0;year OS in multivariable analysis (<i>p</i>-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.</p>

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Genetic landscape of pediatric acute myeloid leukemia in Taiwan

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月7日

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  • Zhongshan Cheng,
  • Sung-Liang Yu,
  • Chih-Hsiang Yu,
  • Ti-Cheng Chang,
  • Ya-Hsuan Chang,
  • Shiann-Tarng Jou,
  • Meng-Yao Lu,
  • Kai-Hsin Lin,
  • Hsiu-Hao Chang,
  • Shu-Wei Chou,
  • Ze-Shiang Lin,
  • Chieh-Wen Kuo,
  • Phooi-Theng Liew,
  • Chia-Jui Du,
  • Chien-Yu Lin,
  • Yu-Ling Ni,
  • Hsuan-Yu Chen,
  • Dong-Tsamn Lin,
  • Shu-Wha Lin,
  • Gang Wu,
  • Ching-Hon Pui,
  • Yung-Li Yang

摘要

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.