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Nature communications, Oct 2025 |
16
 (
1
),
8964
 DOI:
10.1038/s41467-025-64190-8

The genomic landscape of relapsed infant and childhood KMT2A-rearranged acute leukemia

Ahlgren, Louise; Pilheden, Mattias; Sturesson, Helena; Song, Guangchun; Walsh, Michael P; Yang, Minjun; Maillard, Maud; Zhao, Huanbin; Cheng, Zhongshan; Singh, Varsha; Castor, Anders; Pronk, Cornelis Jan; Marquart, Hanne Vibeke; Lausen, Birgitte; Schneider, Pauline; Barbany, Gisela; Pokrovskaja Tamm, Katja; Abrahamsson, Jonas; Lohi, Olli; Fogelstrand, Linda; Menendez, Pablo; Pieters, Rob; Zhang, Jinghui; Lindkvist-Petersson, Karin; Yang, Jun J; Gruber, Tanja A; Stam, Ronald W; Ma, Jing; Hagström-Andersson, Anna K
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Abstract
To study the mechanisms of relapse in KMT2A-rearranged (KMT2A-r) acute lymphoblastic (ALL) and acute myeloid leukemia (AML), we performed whole-genome and exome sequencing of infants and children with relapsed ALL/AML (n = 36), and longitudinal deep-sequencing of 257 samples in 30 patients. Somatic alterations in drug-response genes, most commonly in TP53 and IKZF1 (64%), were highly enriched in early relapse ALL (79%, 9-36 months after diagnosis), but rare in very early relapse ALL (
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