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

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 new insights into the mechanisms of relapse in this highly lethal form of pediatric acute leukemia.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001015662	Sequencing data of leukemic samples included in study. Including WES, WGS and targeted sequencing files from patients at diagnosis, remission and at relapse. The dataset includes samples from 52 pediatric patients, totaling 311 samples.	Illumina HiSeq X Illumina MiSeq Illumina NovaSeq 6000 NextSeq 500	302

Publications	Citations
The genomic landscape of relapsed infant and childhood KMT2A-rearranged acute leukemia. Ahlgren L, Pilheden M, Sturesson H, Song G, Walsh MP, Yang M, Maillard M, Zhao H, Cheng Z, Singh V, Castor A, Pronk CJ, Marquart HV, Lausen B, Schneider P, Barbany G, Pokrovskaja Tamm K, Abrahamsson J, Lohi O, Fogelstrand L, Menendez P, Pieters R, Zhang J, Lindkvist-Petersson K, Yang JJ, Gruber TA, Stam RW, Ma J, Hagström-Andersson AK. Nat Commun 16: 2025 8964	1

Publications

Citations

The genomic landscape of relapsed infant and childhood KMT2A-rearranged acute leukemia.
Ahlgren L, Pilheden M, Sturesson H, Song G, Walsh MP, Yang M, Maillard M, Zhao H, Cheng Z, Singh V, Castor A, Pronk CJ, Marquart HV, Lausen B, Schneider P, Barbany G, Pokrovskaja Tamm K, Abrahamsson J, Lohi O, Fogelstrand L, Menendez P, Pieters R, Zhang J, Lindkvist-Petersson K, Yang JJ, Gruber TA, Stam RW, Ma J, Hagström-Andersson AK. Nat Commun 16: 2025 8964