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The evolution of hematopoietic cells under cancer therapy

Author

Listed:
  • 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
    Universitat Pompeu Fabra)

  • Nuria Lopez-Bigas

    (The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

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.

Suggested Citation

  • Oriol Pich & Albert Cortes-Bullich & Ferran Muiños & Marta Pratcorona & Abel Gonzalez-Perez & Nuria Lopez-Bigas, 2021. "The evolution of hematopoietic cells under cancer therapy," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24858-3
    DOI: 10.1038/s41467-021-24858-3
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    Cited by:

    1. Eline J. M. Bertrums & Jurrian K. Kanter & Lucca L. M. Derks & Mark Verheul & Laurianne Trabut & Markus J. Roosmalen & Henrik Hasle & Evangelia Antoniou & Dirk Reinhardt & Michael N. Dworzak & Nora Mü, 2024. "Selective pressures of platinum compounds shape the evolution of therapy-related myeloid neoplasms," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Ewart Kuijk & Onno Kranenburg & Edwin Cuppen & Arne Van Hoeck, 2022. "Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. Kitty Sherwood & Joseph C. Ward & Ignacio Soriano & Lynn Martin & Archie Campbell & Raheleh Rahbari & Ioannis Kafetzopoulos & Duncan Sproul & Andrew Green & Julian R. Sampson & Alan Donaldson & Kai-Re, 2023. "Germline de novo mutations in families with Mendelian cancer syndromes caused by defects in DNA repair," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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