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. (2025)
Avaa tiedosto
Lataukset:
2025
Nature Communications
8964
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-2025103010265
https://urn.fi/URN:NBN:fi:tuni-2025103010265
Kuvaus
Peer reviewed
Tiivistelmä
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.
Kokoelmat
- TUNICRIS-julkaisut [26203]