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

Louise Ahlgren, Mattias Pilheden, Helena Sturesson, Guangchun Song, Michael P. Walsh, Minjun Yang, Maud Maillard, Huanbin Zhao, Zhongshan Cheng, Varsha Singh, Anders Castor, Cornelis Jan Pronk, Hanne Vibeke Marquart, Birgitte Lausen, Pauline Schneider, Gisela Barbany, Katja Pokrovskaja Tamm, Jonas Abrahamsson, Olli Lohi, Linda Fogelstrand, Pablo Menendez, Rob Pieters, Jinghui Zhang, Karin Lindkvist-Petersson, Jun J. Yang, Tanja A. Gruber, Ronald W. Stam, Jing Ma and Anna K. Hagström-Andersson ()
Additional contact information
Louise Ahlgren: Lund University
Mattias Pilheden: Lund University
Helena Sturesson: Lund University
Guangchun Song: St. Jude Children’s Research Hospital
Michael P. Walsh: St. Jude Children’s Research Hospital
Minjun Yang: Lund University
Maud Maillard: St Jude Children’s Research Hospital
Huanbin Zhao: St Jude Children’s Research Hospital
Zhongshan Cheng: St Jude Children’s Research Hospital
Varsha Singh: Lund University
Anders Castor: Skåne University Hospital
Cornelis Jan Pronk: Skåne University Hospital
Hanne Vibeke Marquart: Rigshospitalet
Birgitte Lausen: University of Copenhagen
Pauline Schneider: Princess Máxima Center for Pediatric Oncology
Gisela Barbany: Karolinska Institutet
Katja Pokrovskaja Tamm: Karolinska Institutet
Jonas Abrahamsson: University of Gothenburg
Olli Lohi: Tampere University Hospital
Linda Fogelstrand: Department of Clinical Chemistry
Pablo Menendez: University of Barcelona
Rob Pieters: Princess Máxima Center for Pediatric Oncology
Jinghui Zhang: St. Jude Children’s Research Hospital
Karin Lindkvist-Petersson: Lund University
Jun J. Yang: St Jude Children’s Research Hospital
Tanja A. Gruber: Stanford University School of Medicine
Ronald W. Stam: Princess Máxima Center for Pediatric Oncology
Jing Ma: St. Jude Children’s Research Hospital
Anna K. Hagström-Andersson: Lund University

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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 (

Date: 2025
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DOI: 10.1038/s41467-025-64190-8

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