Year: 2025
Type: article
Study design: Observational Study
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 (<9 months, 9%). A marked chemotherapy-exposure signature was detected for mutations in early relapse ALL but not in very early ALL or AML relapse, in line with different mechanisms of relapse. Longitudinal analyses could track residual leukemia cells, clonal drug responses, and the upcoming relapse. These results highlight that KMT2A-r ALL and AML evade therapy differently and provide insights into the mechanisms of relapse in this highly lethal form of pediatric acute leukemia.
Source: Nature Communications
Authors: 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, Anna K. Hagström-Andersson
Institutions: Lund University, St. Jude Children's Research Hospital, Skåne University Hospital, University of Copenhagen, Rigshospitalet, Princess Máxima Center, Karolinska Institutet, University of Gothenburg, Tampere University, Tampere University Hospital, University of Tampere, Sahlgrenska University Hospital, Region Västra Götaland, Institució Catalana de Recerca i Estudis Avançats, Instituto de Salud Carlos III, Josep Carreras Leukaemia Research Institute, Centro de Investigación Biomédica en Red de Cáncer, Universitat de Barcelona, Stanford Medicine, Stanford University
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4414960466