The evolution of relapse of adult T cell acute lymphoblastic leukemia

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• dc.contributor.author Sentís, Inés
• dc.contributor.author González, Santi
• dc.contributor.author Genescà, Eulalia
• dc.contributor.author García Hernández, Violeta
• dc.contributor.author Muiños, Ferran
• dc.contributor.author González, Celia
• dc.contributor.author López Arribillaga, Erika, 1986-
• dc.contributor.author González, Jessica
• dc.contributor.author Fernández-Ibarrondo, Lierni
• dc.contributor.author Mularoni, Loris
• dc.contributor.author Espinosa-Anke, Luis
• dc.contributor.author Bellosillo Paricio, Beatriz
• dc.contributor.author Ribera, Josep Maria
• dc.contributor.author Bigas Salvans, Anna
• dc.contributor.author Gonzalez-Perez, Abel
• dc.contributor.author López Bigas, Núria
• dc.date.accessioned 2021-01-27T06:50:19Z
• dc.date.available 2021-01-27T06:50:19Z
• dc.date.issued 2020
• dc.description.abstract Background: Adult T cell acute lymphoblastic leukemia (T-ALL) is a rare disease that affects less than 10 individuals in one million. It has been less studied than its cognate pediatric malignancy, which is more prevalent. A higher percentage of the adult patients relapse, compared to children. It is thus essential to study the mechanisms of relapse of adult T-ALL cases. Results: We profile whole-genome somatic mutations of 19 primary T-ALLs from adult patients and the corresponding relapse malignancies and analyze their evolution upon treatment in comparison with 238 pediatric and young adult ALL cases. We compare the mutational processes and driver mutations active in primary and relapse adult T-ALLs with those of pediatric patients. A precise estimation of clock-like mutations in leukemic cells shows that the emergence of the relapse clone occurs several months before the diagnosis of the primary T-ALL. Specifically, through the doubling time of the leukemic population, we find that in at least 14 out of the 19 patients, the population of relapse leukemia present at the moment of diagnosis comprises more than one but fewer than 108 blasts. Using simulations, we show that in all patients the relapse appears to be driven by genetic mutations. Conclusions: The early appearance of a population of leukemic cells with genetic mechanisms of resistance across adult T-ALL cases constitutes a challenge for treatment. Improving early detection of the malignancy is thus key to prevent its relapse.
• dc.description.sponsorship The authors would like to thank the Asociación Española Contra el Cáncer (AECC) for financially supporting this project (GC16173697BIGA). N.L.-B. acknowledges funding from the European Research Council (consolidator grant 682398) and the ERDF/Spanish Ministry of Science, Innovation and Universities–Spanish State Research Agency/DamReMap Project (RTI2018-094095-B-I00). S. G work is supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 754510. I. S is supported by FPI fellowship from Spanish Ministry of Economy and Competitiveness (project reference SAF2015-66084-R). V.G-H. is supported by the AECC (project reference GC16173697BIGA-9). IRB Barcelona is a recipient of a Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO; Government of Spain) and is supported by CERCA (Generalitat de Catalunya).
• dc.format.mimetype application/pdf
• dc.identifier.citation Sentís I, Gonzalez S, Genescà E, García-Hernández V, Muiños F, Gonzalez C, López-Arribillaga E, Gonzalez J, Fernandez-Ibarrondo L, Mularoni L, Espinosa L, Bellosillo B, Ribera JM, Bigas A, Gonzalez-Perez A, Lopez-Bigas N. The evolution of relapse of adult T cell acute lymphoblastic leukemia. Genome Biol. 2020; 21(1):284. DOI: 10.1186/s13059-020-02192-z
• dc.identifier.doi http://dx.doi.org/10.1186/s13059-020-02192-z
• dc.identifier.issn 1474-7596
• dc.identifier.uri http://hdl.handle.net/10230/46281
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof Genome Biol. 2020; 21(1):284
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/682398
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/754510
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-66084-R
• dc.rights © The Author(s). 2020 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data ma
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword ALL relapse
• dc.subject.keyword Adult acute lymphoblastic leukemia
• dc.subject.keyword Evolution of leukemia relapse
• dc.subject.keyword T-ALL
• dc.subject.keyword T-ALL evolution under therapy
• dc.title The evolution of relapse of adult T cell acute lymphoblastic leukemia
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion