B 细胞急性淋巴细胞白血病 (B-ALL) 是全球范围内儿童癌症相关死亡率的主要原因。这种疾病最传统形式的发展被认为是通过受不同类型风险因素影响的两个不同步骤进行的。第一步是由遗传损伤引起的，这种损伤可能是在出生前获得的，将健康细胞转化为白血病前期细胞，这种细胞在第二步发生之前一直保持不变。儿童出生后接触的不同危险因素将引发白血病发展的必要下一步。回顾 B-ALL 逐步进展的小鼠模型有助于识别导致疾病风险的环境和遗传因素。这些模型的最新证据表明，特定的环境风险因素，例如常见感染或肠道微生物群失调，会诱发免疫应激，驱动白血病前期细胞转化为完全转化的白血病细胞，并含有遗传改变。这些模型可以作为研究白血病前期事件机制的宝贵工具，并有助于开发儿童白血病的预防方法。在这里，我们讨论从小鼠模型中学到的关于遗传和环境风险因素对儿童 B-ALL 进化的影响的现有知识，以及如何通过干扰白血病前期细胞来预防 B-ALL。版权所有 © 2023 Casado-García，伊西德罗-埃尔南德斯、阿莱曼-阿特亚加、鲁伊斯-科尔索、列斯科、普列托-马托斯、桑切斯、桑切斯-加西亚和维森特-杜埃尼亚斯。

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