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 in utero from early hematopoietic stem/progenitor cells (HSPCs), yet its impact on early hematopoiesis...

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Detalles Bibliográficos
Autores: Thampi, N, Calvo, C, Rodríguez-Cortez, V, Martínez-Moreno, A, Roca-Ho, H, Vinyoles, M, Bueno, C, Espinosa-Aroca, L, Pablo-Fontecha, V, Camps, J, de la Fuente-gonzález, A, Puente, XS, Sole, F, Foijer, F, Ndez, PM, Molina, O
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:dnet:r-fsjd______::4ca7f9365b3c2ea9d72d89489d3a253d
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=30252
Access Level:acceso abierto
Palabra clave:B cell acute lymphoblastic leukemia
B-ALL
CP: cancer
CP: cell biology
HSPCs
aneuploidy
hematopoietic stem/progenitor cells
hyperdiploidy
Descripción
Sumario: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 in utero 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 in vitro, 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.

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