Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones

Aneuploidy is a hallmark of cancer but often reduces cellular fitness. In childhood B cell acute lymphoblastic leukemia (cB-ALL), hyperdiploidy is the most common cytogenetic abnormality and arises <em>in utero</em> from early hematopoietic stem/progenitor cells (HSPCs), yet its impact o...

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Autores: Thampi, Namitha, Calvo, Cristina, Rodríguez Cortez, Virginia Carolina, Martínez-Moreno, Alba, Roca-Ho, Heleia, Vinyoles, Meritxell, Bueno, Clara, Espinosa-Aroca, Lady, Pablo-Fontecha, Verónica, Camps, Jordi, Fuente-González, A. de la, Puente, Xose S, Solé, Francesc, Foijer, Floris, Menéndez Buján, Pablo, Molina, Òscar
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:dnet:recercat____::7b0c92b75151cf53ffa5b71b6e6d1019
Acesso em linha:https://hdl.handle.net/2445/228727
Access Level:acceso abierto
Palavra-chave:Leucèmia limfocítica crònica
Càncer en els infants
Chronic lymphocytic leukemia
Cancer in children
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spelling Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clonesThampi, NamithaCalvo, CristinaRodríguez Cortez, Virginia CarolinaMartínez-Moreno, AlbaRoca-Ho, HeleiaVinyoles, MeritxellBueno, ClaraEspinosa-Aroca, LadyPablo-Fontecha, VerónicaCamps, JordiFuente-González, A. de laPuente, Xose SSolé, FrancescFoijer, FlorisMenéndez Buján, PabloMolina, ÒscarLeucèmia limfocítica crònicaCàncer en els infantsChronic lymphocytic leukemiaCancer in childrenAneuploidy is a hallmark of cancer but often reduces cellular fitness. In childhood B cell acute lymphoblastic leukemia (cB-ALL), hyperdiploidy is the most common cytogenetic abnormality and arises <em>in utero</em> from early hematopoietic stem/progenitor cells (HSPCs), yet its impact on early hematopoiesis remains unclear. We model two proposed routes to hyperdiploidy, chromosome mis-segregation and cytokinesis failure, by transiently exposing human fetal liver-derived HSPCs to reversine or cytochalasin D. Induced hyperdiploidy impaired fitness and delayed differentiation <em>in vitro</em>, causing hyperdiploid cells to be rapidly outcompeted by euploid counterparts. Nonetheless, hyperdiploid cells engrafted immunodeficient mice, where rare clones persisted long term and acquired non-random chromosomal gains frequently observed in cB-ALL. Despite this persistence, they did not initiate leukemia. These findings support a two-step model in which hyperdiploid fetal clones require additional perinatal/postnatal events for malignant transformation. Our work establishes a valuable human model for studying early aneuploidy-driven events in childhood leukemia.Elsevier2026202620262026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion34 p.application/pdfhttps://hdl.handle.net/2445/228727Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.celrep.2026.117173Cell Reports, 2026, vol. 45, num.4https://doi.org/10.1016/j.celrep.2026.117173cc-by-nc-nd (c) Thampi, Namitha et al., 2026https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:recercat____::7b0c92b75151cf53ffa5b71b6e6d10192026-05-29T05:05:01Z
dc.title.none.fl_str_mv Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones
title Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones
spellingShingle Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones
Thampi, Namitha
Leucèmia limfocítica crònica
Càncer en els infants
Chronic lymphocytic leukemia
Cancer in children
title_short Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones
title_full Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones
title_fullStr Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones
title_full_unstemmed Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones
title_sort Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones
dc.creator.none.fl_str_mv Thampi, Namitha
Calvo, Cristina
Rodríguez Cortez, Virginia Carolina
Martínez-Moreno, Alba
Roca-Ho, Heleia
Vinyoles, Meritxell
Bueno, Clara
Espinosa-Aroca, Lady
Pablo-Fontecha, Verónica
Camps, Jordi
Fuente-González, A. de la
Puente, Xose S
Solé, Francesc
Foijer, Floris
Menéndez Buján, Pablo
Molina, Òscar
author Thampi, Namitha
author_facet Thampi, Namitha
Calvo, Cristina
Rodríguez Cortez, Virginia Carolina
Martínez-Moreno, Alba
Roca-Ho, Heleia
Vinyoles, Meritxell
Bueno, Clara
Espinosa-Aroca, Lady
Pablo-Fontecha, Verónica
Camps, Jordi
Fuente-González, A. de la
Puente, Xose S
Solé, Francesc
Foijer, Floris
Menéndez Buján, Pablo
Molina, Òscar
author_role author
author2 Calvo, Cristina
Rodríguez Cortez, Virginia Carolina
Martínez-Moreno, Alba
Roca-Ho, Heleia
Vinyoles, Meritxell
Bueno, Clara
Espinosa-Aroca, Lady
Pablo-Fontecha, Verónica
Camps, Jordi
Fuente-González, A. de la
Puente, Xose S
Solé, Francesc
Foijer, Floris
Menéndez Buján, Pablo
Molina, Òscar
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Leucèmia limfocítica crònica
Càncer en els infants
Chronic lymphocytic leukemia
Cancer in children
topic Leucèmia limfocítica crònica
Càncer en els infants
Chronic lymphocytic leukemia
Cancer in children
description Aneuploidy is a hallmark of cancer but often reduces cellular fitness. In childhood B cell acute lymphoblastic leukemia (cB-ALL), hyperdiploidy is the most common cytogenetic abnormality and arises <em>in utero</em> from early hematopoietic stem/progenitor cells (HSPCs), yet its impact on early hematopoiesis remains unclear. We model two proposed routes to hyperdiploidy, chromosome mis-segregation and cytokinesis failure, by transiently exposing human fetal liver-derived HSPCs to reversine or cytochalasin D. Induced hyperdiploidy impaired fitness and delayed differentiation <em>in vitro</em>, causing hyperdiploid cells to be rapidly outcompeted by euploid counterparts. Nonetheless, hyperdiploid cells engrafted immunodeficient mice, where rare clones persisted long term and acquired non-random chromosomal gains frequently observed in cB-ALL. Despite this persistence, they did not initiate leukemia. These findings support a two-step model in which hyperdiploid fetal clones require additional perinatal/postnatal events for malignant transformation. Our work establishes a valuable human model for studying early aneuploidy-driven events in childhood leukemia.
publishDate 2026
dc.date.none.fl_str_mv 2026
2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/228727
url https://hdl.handle.net/2445/228727
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2026.117173
Cell Reports, 2026, vol. 45, num.4
https://doi.org/10.1016/j.celrep.2026.117173
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Thampi, Namitha et al., 2026
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Thampi, Namitha et al., 2026
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 34 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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