Deletion 9p drives B-ALL through the heterozygous inactivation of Pax5 and Cd72 in pre-leukemic cells
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 exhibit 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 two contiguous genes, Pax5 and Cd72, drives B-cell leukemogenesis.
Authors
- Maria Begoña García-Cenador
- Belén Ruiz-Corzo
- Óscar Blanco (ORCID: https://orcid.org/0000-0002-2667-0489)
- César Cobaleda (ORCID: https://orcid.org/0000-0003-3807-9204)
- Susana Riesco (ORCID: https://orcid.org/0000-0001-5443-8786)
- Jorge Martínez-Cano (ORCID: https://orcid.org/0000-0001-6809-5489)
- Ana Casado-García (ORCID: https://orcid.org/0000-0003-1510-1499)
- Carolina Vicente‐Dueñas (ORCID: https://orcid.org/0000-0002-5401-8295)
- Javier De Las Rivas (ORCID: https://orcid.org/0000-0002-0984-9946)
- Andrea López-Álvarez de Neyra (ORCID: https://orcid.org/0009-0000-0430-312X)
- Paula Somoza-Cotillas
- Francisco Javier Garcia-Criado
- Pablo Prieto-Matos
- Manuel Ramírez-Orellana
- Ninad Oak
- Diego Alonso-López
- Kim E. Nichols
- Alberto Orfao
- Elena G. Sánchez
- Isidro Sánchez-García
- Alba Pérez-Pons
Institutions
- St. Jude Children's Research Hospital (US)
- Consejo Superior de Investigaciones Científicas (ES)
- Universidad de Salamanca (ES)
- Hospital Infantil Universitario Niño Jesús (ES)
- Instituto de Investigación Biomédica de Salamanca (ES)
- Centro de Investigación del Cáncer (ES)
- Centro de Biología Molecular Severo Ochoa (ES)
- Universidad Autónoma de Madrid (ES)
Publication Details
- Journal
- JCI Insight
- Published
- 2026-02-17
- DOI
- https://doi.org/10.1172/jci.insight.199464
- Primary Topic
- Acute Lymphoblastic Leukemia research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
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