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

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 re...

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Autores principales: Coorens, Tim H. H., Collord, Grace, Treger, Taryn D., Adams, Stuart, Mitchell, Emily, Newman, Barbara, Getz, Gad, Godfrey, Anna L., Bartram, Jack, Behjati, Sam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2023
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447231/
https://www.ncbi.nlm.nih.gov/pubmed/37474833
http://dx.doi.org/10.1038/s43018-023-00604-0
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author Coorens, Tim H. H.
Collord, Grace
Treger, Taryn D.
Adams, Stuart
Mitchell, Emily
Newman, Barbara
Getz, Gad
Godfrey, Anna L.
Bartram, Jack
Behjati, Sam
author_facet Coorens, Tim H. H.
Collord, Grace
Treger, Taryn D.
Adams, Stuart
Mitchell, Emily
Newman, Barbara
Getz, Gad
Godfrey, Anna L.
Bartram, Jack
Behjati, Sam
author_sort Coorens, Tim H. H.
collection PubMed
description 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.
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spelling pubmed-104472312023-08-25 Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy Coorens, Tim H. H. Collord, Grace Treger, Taryn D. Adams, Stuart Mitchell, Emily Newman, Barbara Getz, Gad Godfrey, Anna L. Bartram, Jack Behjati, Sam Nat Cancer Brief Communication 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. Nature Publishing Group US 2023-07-20 2023 /pmc/articles/PMC10447231/ /pubmed/37474833 http://dx.doi.org/10.1038/s43018-023-00604-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Communication
Coorens, Tim H. H.
Collord, Grace
Treger, Taryn D.
Adams, Stuart
Mitchell, Emily
Newman, Barbara
Getz, Gad
Godfrey, Anna L.
Bartram, Jack
Behjati, Sam
Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy
title Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy
title_full Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy
title_fullStr Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy
title_full_unstemmed Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy
title_short Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy
title_sort clonal origin of kmt2a wild-type lineage-switch leukemia following car-t cell and blinatumomab therapy
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447231/
https://www.ncbi.nlm.nih.gov/pubmed/37474833
http://dx.doi.org/10.1038/s43018-023-00604-0
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