The evolution of relapse of adult T cell acute lymphoblastic leukemia
Sentís, I. (Institut de Recerca Biomèdica)
González, S. (Institut de Recerca Biomèdica)
Genescà, Eulàlia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
García-Hernández, Violeta (Institut Hospital del Mar d'Investigacions Mèdiques)
Muiños, Ferran (Institut de Recerca Biomèdica)
González Gil, Celia. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
López-Arribillaga, E. (Institut de Recerca Biomèdica)
González, Jéssica (Institut Hospital del Mar d'Investigacions Mèdiques)
Fernández Ibarrondo, Lierni (Institut Hospital del Mar d'Investigacions Mèdiques)
Mularoni, L. (CMR[B] Center of Regenerative Medicine)
Espinosa, Lluís (Institut Hospital del Mar d'Investigacions Mèdiques)
Bellosillo Paricio, Beatriz (Institut Hospital del Mar d'Investigacions Mèdiques)
Ribera, Jose-Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Bigas Salvans, Anna (Institut Hospital del Mar d'Investigacions Mèdiques)
González-Pérez, A (Universitat Pompeu Fabra)
Lopez-Bigas, N. (Institució Catalana de Recerca i Estudis Avançats)
Universitat Autònoma de Barcelona

Date:	2020
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 10 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.
Grants:	Ministerio de Economía y Competitividad SAF2015-66084-R Ministerio de Ciencia e Innovación RTI2018-094095-B-I00 European Commission 754510
Note:	Altres ajuts: The authors would like to thank the Asociación Española Contra el Cáncer (AECC) for financially supporting this project (GC16173697BIGA). V.G-H. is supported by the AECC (project reference GC16173697BIGA-9). IRB is supported by CERCA (Generalitat de Catalunya).
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:	ALL relapse ; Adult acute lymphoblastic leukemia ; Evolution of leukemia relapse ; T-ALL ; T-ALL evolution under therapy
Published in:	Genome biology, Vol. 21 Núm. 1 (december 2020) , p. 284, ISSN 1474-760X

DOI: 10.1186/s13059-020-02192-z
PMID: 33225950

24 p, 2.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles