The evolution of hematopoietic cells under cancer therapy

Oriol Pich, Albert Cortes-Bullich, Ferran Muiños, Marta Pratcorona, Abel Gonzalez-Perez () and Nuria Lopez-Bigas ()
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Oriol Pich: The Barcelona Institute of Science and Technology
Albert Cortes-Bullich: Hospital Santa Creu i Sant Pau
Ferran Muiños: The Barcelona Institute of Science and Technology
Marta Pratcorona: Hospital Santa Creu i Sant Pau
Abel Gonzalez-Perez: The Barcelona Institute of Science and Technology
Nuria Lopez-Bigas: The Barcelona Institute of Science and Technology

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Chemotherapies may increase mutagenesis of healthy cells and change the selective pressures in tissues, thus influencing their evolution. However, their contributions to the mutation burden and clonal expansions of healthy somatic tissues are not clear. Here, exploiting the mutational footprint of some chemotherapies, we explore their influence on the evolution of hematopoietic cells. Cells of Acute Myeloid Leukemia (AML) secondary to treatment with platinum-based drugs show the mutational footprint of these drugs, indicating that non-malignant blood cells receive chemotherapy mutations. No trace of the 5-fluorouracil (5FU) mutational signature is found in AMLs secondary to exposure to 5FU, suggesting that cells establishing the leukemia could be quiescent during treatment. Using the platinum-based mutational signature as a barcode, we determine that the clonal expansion originating the secondary AMLs begins after the start of the cytotoxic treatment. Its absence in clonal hematopoiesis cases is consistent with the start of the clonal expansion predating the exposure to platinum-based drugs.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24858-3

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DOI: 10.1038/s41467-021-24858-3

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