Coorens, THH;
Collord, G;
Treger, TD;
Adams, S;
Mitchell, E;
Newman, B;
Getz, G;
... Behjati, S; + view all
(2023)
Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy.
Nature Cancer
, 4
(8)
pp. 1095-1101.
10.1038/s43018-023-00604-0.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s43018-023-00604-0 |
| Publisher version: | http://dx.doi.org/10.1038/s43018-023-00604-0 |
| Language: | English |
| Additional information: | 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/. |
| Keywords: | Child, Female, Humans, Leukemia, Myeloid, Acute, Antibodies, Bispecific, Precursor Cell Lymphoblastic Leukemia-Lymphoma, T-Lymphocytes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10187231 |
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