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Infectious triggers and novel therapeutic opportunities in childhood B cell leukaemia

Nature Reviews Immunology volume 21, pages 570–581 (2021)Cite this article

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Abstract

B cell acute lymphoblastic leukaemia (B-ALL) is the most common form of childhood cancer. Although treatment has advanced remarkably in the past 50 years, it still fails in ~20% of patients. Recent studies revealed that more than 5% of healthy newborns carry preleukaemic clones that originate in utero, but only a small percentage of these carriers will progress to overt B-ALL. The drivers of progression are unclear, but B-ALL incidence seems to be increasing in parallel with the adoption of modern lifestyles. Emerging evidence shows that a major driver for the conversion from the preleukaemic state to the B-ALL state is exposure to immune stressors, such as infection. Here, we discuss our current understanding of the environmental triggers and genetic predispositions that may lead to B-ALL, highlighting lessons from epidemiology, the clinic and animal models, and identifying priority areas for future research.

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Fig. 1: Genetic vulnerability of B-ALL preleukaemic clones.
Fig. 2: A unified model for childhood B-ALL development.

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Acknowledgements

The authors thank all the scientists who have contributed to this exciting field and apologize to those colleagues they were unable to cite. They thank the reviewers for their suggestions and comments, and A. Borkhardt, U. Fischer and all members of their groups for their generosity and useful discussions before the preparation of the manuscript, where several of the concepts examined have been investigated together. Research at C.C.’s laboratory was partially supported by the European Regional Development Fund (FEDER)/MINECO (SAF2017-83061-R), Fundación Ramón Areces and a research contract with Fundación Síndrome de Wolf-Hirschhorn o 4p-. Institutional grants from Fundación Ramón Areces and Banco de Santander to Centro de Biología Molecular Severo Ochoa are also acknowledged. The C.C. and C.V.-D. laboratories are members of the EU COST Action LEGEND (CA16223). Research in the C.V.-D. group is partially supported by an FEDER Miguel Servet grant (CPII19/00024 — AES 2017-2020) from Instituto de Salud Carlos III (Ministerio de Economía y Competitividad), Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III (PI17/00167). Research in the I.S.-G. group is partially supported by the FEDER and by MINECO/FEDER (SAF2015-64420-R), MCIU/AEI/FEDER (RTI2018-093314-B-I00), Junta de Castilla y León (UIC-017, CSI001U16, CSI234P18 and CSI144P20), the German Carreras Foundation (DJCLS 07R/2019) and Fundacion Unoentrecienmil (CUNINA project). The I.S.-G. laboratory is a member of EuroSyStem and the DECIDE Network funded by the European Union under the Seventh Framework Programme. C.V.-D. and I.S.-G. have been supported by the German Federal Office for Radiation Protection (BfS) (FKZ: 3618S32274).

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Authors and Affiliations

  1. Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa, CSIC and Universidad Autónoma de Madrid, Madrid, Spain

    Cesar Cobaleda

  2. Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain

    Carolina Vicente-Dueñas & Isidro Sanchez-Garcia

  3. Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC and Universidad de Salamanca, Salamanca, Spain

    Isidro Sanchez-Garcia

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  1. Cesar Cobaleda
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  2. Carolina Vicente-Dueñas
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  3. Isidro Sanchez-Garcia
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The authors contributed equally to all aspects of the article.

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Correspondence to Cesar Cobaleda or Isidro Sanchez-Garcia.

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Nature Reviews Immunology thanks C. Mullighan, M. Witkowski and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Cobaleda, C., Vicente-Dueñas, C. & Sanchez-Garcia, I. Infectious triggers and novel therapeutic opportunities in childhood B cell leukaemia. Nat Rev Immunol 21, 570–581 (2021). https://doi.org/10.1038/s41577-021-00505-2

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