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Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID

Author

Listed:
  • Guillermo Rodríguez-Hernández

    (CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Friederike V. Opitz

    (Heinrich Heine University)

  • Pilar Delgado

    (B Cell Biology Lab, Centro Nacional de Investigaciones Cardiovasculares)

  • Carolin Walter

    (University of Muenster)

  • Ángel F. Álvarez-Prado

    (B Cell Biology Lab, Centro Nacional de Investigaciones Cardiovasculares)

  • Inés González-Herrero

    (CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Franziska Auer

    (Heinrich Heine University
    City of Hope Comprehensive Cancer Center)

  • Ute Fischer

    (Heinrich Heine University)

  • Stefan Janssen

    (Heinrich Heine University)

  • Christoph Bartenhagen

    (University Children’s Hospital of Cologne, Medical Faculty
    University of Cologne)

  • Javier Raboso-Gallego

    (CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Ana Casado-García

    (CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Alberto Orfao

    (Institute of Biomedical Research of Salamanca (IBSAL)
    CIBERON, and Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca)

  • Oscar Blanco

    (Institute of Biomedical Research of Salamanca (IBSAL)
    Universidad de Salamanca)

  • Diego Alonso-López

    (Bioinformatics Unit, Cancer Research Center (CSIC-USAL))

  • Javier De Las Rivas

    (Institute of Biomedical Research of Salamanca (IBSAL)
    Cancer Research Center (CSIC-USAL))

  • Sara González de Tena-Dávila

    (CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Markus Müschen

    (City of Hope Comprehensive Cancer Center)

  • Martin Dugas

    (University of Muenster)

  • Francisco Javier García Criado

    (Institute of Biomedical Research of Salamanca (IBSAL)
    Universidad de Salamanca)

  • María Begoña García Cenador

    (Institute of Biomedical Research of Salamanca (IBSAL)
    Universidad de Salamanca)

  • Carolina Vicente-Dueñas

    (Institute of Biomedical Research of Salamanca (IBSAL))

  • Julia Hauer

    (Heinrich Heine University)

  • Almudena R. Ramiro

    (B Cell Biology Lab, Centro Nacional de Investigaciones Cardiovasculares)

  • Isidro Sanchez-Garcia

    (CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Arndt Borkhardt

    (Heinrich Heine University)

Abstract

The prerequisite to prevent childhood B-cell acute lymphoblastic leukemia (B-ALL) is to decipher its etiology. The current model suggests that infection triggers B-ALL development through induction of activation-induced cytidine deaminase (AID; also known as AICDA) in precursor B-cells. This evidence has been largely acquired through the use of ex vivo functional studies. However, whether this mechanism governs native non-transplant B-ALL development is unknown. Here we show that, surprisingly, AID genetic deletion does not affect B-ALL development in Pax5-haploinsufficient mice prone to B-ALL upon natural infection exposure. We next test the effect of premature AID expression from earliest pro-B-cell stages in B-cell transformation. The generation of AID off-target mutagenic activity in precursor B-cells does not promote B-ALL. Likewise, known drivers of human B-ALL are not preferentially targeted by AID. Overall these results suggest that infections promote B-ALL through AID-independent mechanisms, providing evidence for a new model of childhood B-ALL development.

Suggested Citation

  • Guillermo Rodríguez-Hernández & Friederike V. Opitz & Pilar Delgado & Carolin Walter & Ángel F. Álvarez-Prado & Inés González-Herrero & Franziska Auer & Ute Fischer & Stefan Janssen & Christoph Barten, 2019. "Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13570-y
    DOI: 10.1038/s41467-019-13570-y
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    Cited by:

    1. Marta Isidro-Hernández & Ana Casado-García & Ninad Oak & Silvia Alemán-Arteaga & Belén Ruiz-Corzo & Jorge Martínez-Cano & Andrea Mayado & Elena G. Sánchez & Oscar Blanco & Ma Luisa Gaspar & Alberto Or, 2023. "Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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