Lessons from mouse models in the impact of risk factors on the genesis of childhood B-cell leukemia

Frontiers in Immunology

Immunology

Susana Riesco¹  Carolina Vicente-Dueñas¹  Pablo Prieto-Matos¹  Silvia Alemán-Arteaga²  Belén Ruiz-Corzo²  Isidro Sánchez-García²  Ana Casado-García²  Marta Isidro-Hernández²  Lucía Sánchez³ 

[1] Department of Pediatrics, Hospital Universitario de Salamanca, Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain;Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Salamanca, Salamanca, Spain;Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain;School of Law, University of Salamanca, Salamanca, Spain;

关键词: childhood leukemia;    B-ALL;    mouse models;    risk factors;    genetic predisposition;    environmental factors;   

DOI  :  10.3389/fimmu.2023.1285743

 received in 2023-08-30, accepted in 2023-10-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

B-cell acute lymphoblastic leukemia (B-ALL) stands as the primary contributor to childhood cancer-related mortality on a global scale. The development of the most conventional forms of this disease has been proposed to be conducted by two different steps influenced by different types of risk factors. The first step is led by a genetic insult that is presumably acquired before birth that transforms a healthy cell into a preleukemic one, which is maintained untransformed until the second step takes place. This necessary next step to leukemia development will be triggered by different risk factors to which children are exposed after birth. Murine models that recap the stepwise progression of B-ALL have been instrumental in identifying environmental and genetic factors that contribute to disease risk. Recent evidence from these models has demonstrated that specific environmental risk factors, such as common infections or gut microbiome dysbiosis, induce immune stress, driving the transformation of preleukemic cells, and harboring genetic alterations, into fully transformed leukemic cells. Such models serve as valuable tools for investigating the mechanisms underlying preleukemic events and can aid in the development of preventive approaches for leukemia in child. Here, we discuss the existing knowledge, learned from mouse models, of the impact of genetic and environmental risk factors on childhood B-ALL evolution and how B-ALL prevention could be reached by interfering with preleukemic cells.

【 授权许可】

Unknown   
Copyright © 2023 Casado-García, Isidro-Hernández, Alemán-Arteaga, Ruiz-Corzo, Riesco, Prieto-Matos, Sánchez, Sánchez-García and Vicente-Dueñas