The evolution of hematopoietic cells under cancer therapy
Pich, Oriol (Institut de Recerca Biomèdica)
Cortes-Bullich, A. (Institut d'Investigació Biomèdica Sant Pau)
Muiños, Ferran (Institut de Recerca Biomèdica)
Pratcorona, Marta (Institut d'Investigació Biomèdica Sant Pau)
Gonzalez-Perez, A. (Universitat Pompeu Fabra)
Lopez-Bigas, N. (Institució Catalana de Recerca i Estudis Avançats)

Date:	2021
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.
Grants:	European Research Council 682398 Ministerio de Ciencia, Innovación y Universidades RTI2018-094095-B-I00
Note:	Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Asociación Española Contra el Cáncer (AECC) (GC16173697BIGA); Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO; Government of Spain); CERCA (Generalitat de Catalunya); Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia; Barcelona Institute of Science and Technology (BIST); Hartwig Medical Foundation; Center for Personalized Cancer Treatment (CPCT).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Acute Disease ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; Clonal Evolution ; Clone Cells ; Cohort Studies ; Female ; Fluorouracil ; Hematopoiesis ; Humans ; Isocitrate Dehydrogenase ; Leukemia, Myeloid ; Mutagenesis ; Mutation ; Neoplasms, Second Primary ; Platinum ; Tumor Suppressor Protein p53
Published in:	Nature communications, Vol. 12 Núm. 1 (january 2021) , p. 4803, ISSN 2041-1723

DOI: 10.1038/s41467-021-24858-3
PMID: 34376657

11 p, 4.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles