Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones
Por:
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 and Molina, O
Publicada:
28 abr 2026
Ahead of Print:
27 mar 2026
Resumen:
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.
Filiaciones:
Thampi, N:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III, Red Espanola Terapias Avanzadas TERAV, Barcelona, Spain
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Calvo, C:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III, Red Espanola Terapias Avanzadas TERAV, Barcelona, Spain
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Rodríguez-Cortez, V:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III, Red Espanola Terapias Avanzadas TERAV, Barcelona, Spain
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Martínez-Moreno, A:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III, Red Espanola Terapias Avanzadas TERAV, Barcelona, Spain
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Roca-Ho, H:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III, Red Espanola Terapias Avanzadas TERAV, Barcelona, Spain
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Vinyoles, M:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III, Red Espanola Terapias Avanzadas TERAV, Barcelona, Spain
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Bueno, C:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III, Red Espanola Terapias Avanzadas TERAV, Barcelona, Spain
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Espinosa-Aroca, L:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III, Red Espanola Terapias Avanzadas TERAV, Barcelona, Spain
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Pablo-Fontecha, V:
August Pi i Sunyer Biomed Res Inst IDIBAPS, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Camps, J:
August Pi i Sunyer Biomed Res Inst IDIBAPS, Barcelona, Spain
CIBEREHD, Barcelona, Spain
Autonomous Univ Barcelona, Sch Med, Dept Cell Biol Physiol & Immunol, Cell Biol & Med Genet Unit, Barcelona, Spain
de la Fuente-gonzález, A:
Univ Oviedo, Inst Univ Oncol IUOPA, Dept Biochem & Mol Biol, Oviedo, Spain
Puente, XS:
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Univ Oviedo, Inst Univ Oncol IUOPA, Dept Biochem & Mol Biol, Oviedo, Spain
Foijer, F:
Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Ageing ERIBA, Groningen, Netherlands
:
Univ Barcelona, Sch Med & Hlth Sci, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III, Red Espanola Terapias Avanzadas TERAV, Barcelona, Spain
Inst Recerca St Joan Deu PCCB SJD, Pediat Canc Ctr Barcelona, Barcelona, Spain
Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
Molina, O:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
Inst Salud Carlos III, Red Espanola Terapias Avanzadas TERAV, Barcelona, Spain
Inst Salud Carlos III, Spanish Natl Canc Network CIBERONC, Barcelona, Spain
Univ Barcelona, Sch Med & Hlth Sci, Dept Physiol Sci, Genet Sect, Barcelona, Spain
Hosp Germans Trias i Pujol, Catalan Inst Oncol ICO, Josep Carreras Leukemia Res Inst, Badalona, Barcelona, Spain
Hosp Germans Trias i Pujol, Catalan Inst Oncol ICO, Josep Carreras Leukemia Res Inst, Badalona, Barcelona, Spain
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