Deletion of 9p drives B-ALL through heterozygous inactivation of Pax5 and Cd72 in preleukemic cells
Year: 2026
Type: article
Abstract: The contribution of 9p deletion to B cell acute lymphoblastic leukemia (B-ALL) has remained elusive since its discovery more than 40 years ago. Here we show that loss of CD72 is recurrent in B-ALL cases containing PAX5 deletions, and that Cd72 haploinsufficiency drives B-ALL development in Pax5+/- mice. Mechanistically, Cd72+/-;Pax5+/- precursor B cells exhibited an inflammatory transcriptional profile characterized by a decrease in Myd88 expression, a finding that aligns with our previous studies of B-ALL development in Pax5+/- mice following exposure to immune stressors. These combined genomic analyses and functional models provide compelling evidence that co-deletion of 2 contiguous genes, Pax5 and Cd72, drives B cell leukemogenesis.
Source: JCI Insight
Authors: Belén Ruiz-Corzo, Ana Casado-García, Ninad Oak, Paula Somoza-Cotillas, Andrea López-Álvarez de Neyra, Jorge Martínez-Cano, Alba Pérez-Pons, Elena G. Sánchez, Oscar Blanco, Diego Alonso-López, Javier De Las Rivas, Susana Riesco, Pablo Prieto-Matos, Francisco Javier García Criado, María Begoña García Cenador, Alberto Orfao, Manuel Ramírez-Orellana, César Cobaleda, Carolina Vicente-Dueñas, Kim E. Nichols, Isidro Sánchez-García
Institutions: Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca, St. Jude Children's Research Hospital, Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Centro de Investigación del Cáncer, Centro de Investigación Biomédica en Red de Cáncer, Instituto de Biología Molecular y Celular del Cáncer de Salamanca, Hospital Infantil Universitario Niño Jesús, Complejo Hospitalario de Salamanca, Hospital Universitario de La Princesa
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Funders: St. Jude Children's Research Hospital, Fundación Ramón Areces, American Lebanese Syrian Associated Charities, Fundación Científica Asociación Española Contra el Cáncer, Junta de Castilla y León, Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona, National Institutes of Health, Instituto de Salud Carlos III, European Regional Development Fund, Agencia Estatal de Investigación
Awards: G1175115578, G2214816500, G2262748287, G2550080368, Alto peso al nacer, susceptibilidad genética y leucemia infantil de células B, G300979063, G3480869486, G410571670, G425668148, G4258994604, G451917667, G5080475149, G5246448272, G5737029042, G5967599077, Descifrando biomarcadores epigenéticos para identificar portadores preleucémicos en riesgo
OpenAlex ID: W7129532801
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