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ResearchIn-Press PreviewHematologyOncology Open Access | 10.1172/jci.insight.199464

Deletion 9p drives B-ALL through the heterozygous inactivation of Pax5 and Cd72 in pre-leukemic cells

Belén Ruiz-Corzo,1 Ana Casado-García,1 Ninad Oak,2 Paula Somoza-Cotillas,1 Andrea López-Álvarez de Neyra,1 Jorge Martínez-Cano,3 Alba Pérez-Pons,4 Elena G. Sánchez,5 Oscar Blanco,6 Diego Alonso-López,7 Javier De Las Rivas,6 Susana Riesco,6 Pablo Prieto-Matos,6 Francisco Javier Garcia-Criado,6 Maria Begoña Garcia-Cenador,6 Alberto Orfao,4 Manuel Ramírez-Orellana,8 César Cobaleda,3 Carolina Vicente-Dueñas,6 Kim E. Nichols,2 and Isidro Sánchez-García1

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Ruiz-Corzo, B. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Casado-García, A. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Oak, N. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Somoza-Cotillas, P. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by López-Álvarez de Neyra, A. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Martínez-Cano, J. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Pérez-Pons, A. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Sánchez, E. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Blanco, O. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Alonso-López, D. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by De Las Rivas, J. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Riesco, S. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Prieto-Matos, P. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Garcia-Criado, F. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Garcia-Cenador, M. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Orfao, A. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Ramírez-Orellana, M. in: PubMed | Google Scholar |

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Cobaleda, C. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Vicente-Dueñas, C. in: PubMed | Google Scholar

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Nichols, K. in: PubMed | Google Scholar |

1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Campus M. de Unamuno, Salamanca, Spain

2Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America

3Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain

4Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytom, University of Salamanca, Biomedical Research Institute of Salamanca, Salamanca, Spain

5Oncohematology Laboratory, Advance Therapy Unit, Fundación para la Investigación Biomédica del Hospital Universitario Niño Jesús (FIB HUNJ), Madrid, Spain

6Institute of Biomedical Research of Salamanca (IBSAL), Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain

7Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain

8Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús Jesús & Institute of Biomedical Research Hospital Universitario La Princesa, Madrid, Spain

Find articles by Sánchez-García, I. in: PubMed | Google Scholar

Published February 17, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.199464.
Copyright © 2026, Ruiz-Corzo et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 17, 2026 - Version history
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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 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.

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