Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy.

Autor: Coorens THH; Broad Institute of MIT and Harvard, Cambridge, MA, USA. tcoorens@broadinstitute.org., Collord G; Great Ormond Street Hospital for Children, London, UK., Treger TD; Wellcome Sanger Institute, Hinxton, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Department of Paediatrics, University of Cambridge, Cambridge, UK., Adams S; Great Ormond Street Hospital for Children, London, UK., Mitchell E; Wellcome Sanger Institute, Hinxton, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Newman B; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Getz G; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Godfrey AL; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Bartram J; Great Ormond Street Hospital for Children, London, UK., Behjati S; Wellcome Sanger Institute, Hinxton, UK. sb31@sanger.ac.uk.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. sb31@sanger.ac.uk.; Department of Paediatrics, University of Cambridge, Cambridge, UK. sb31@sanger.ac.uk.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2023 Aug; Vol. 4 (8), pp. 1095-1101. Date of Electronic Publication: 2023 Jul 20.
DOI: 10.1038/s43018-023-00604-0
Abstrakt: Children with acute lymphoblastic leukemia (ALL) undergoing anti-CD19 therapy occasionally develop acute myeloid leukemia (AML). The clonal origin of such lineage-switch leukemias 1-4 remains unresolved. Here, we reconstructed the phylogeny of multiple leukemias in a girl who, following multiply relapsed ALL, received anti-CD19 cellular and antibody treatment and subsequently developed AML. Whole genome sequencing unambiguously revealed the AML derived from the initial ALL, with distinct driver mutations that were detectable before emergence. Extensive prior diversification and subsequent clonal selection underpins this fatal lineage switch. Genomic monitoring of primary leukemias and recurrences may predict therapy resistance, especially regarding anti-CD19 treatment.
(© 2023. The Author(s).)
Databáze: MEDLINE
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