Children show a higher incidence of leukaemia compared with young adolescents, yet their cells are less damaged because of their young age. Children with Down syndrome (DS) have an even higher risk of developing leukaemia during the first years of life. The presence of a constitutive trisomy of chromosome 21 (T21) in DS acts as a genetic driver for leukaemia development, however, additional oncogenic mutations are required. Therefore, T21 provides the opportunity to better understand leukaemogenesis in children. Here, we describe the increased risk of leukaemia in DS during childhood from a somatic evolutionary view. According to this idea, cancer is caused by a variation in inheritable phenotypes within cell populations that are subjected to selective forces within the tissue context. We propose a model in which the increased risk of leukaemia in DS children derives from higher rates of mutation accumulation, already present during fetal development, which is further enhanced by changes in selection dynamics within the fetal liver niche. This model could possibly be used to understand the rate-limiting steps of leukaemogenesis early in life.

中文翻译：

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唐氏综合症儿童患白血病的风险增加：体细胞进化观点

与青少年相比，儿童的白血病发病率更高，但他们的细胞由于年龄较小而受到的损害较小。患有唐氏综合症 (DS) 的儿童在出生后头几年患白血病的风险更高。DS 中 21 号染色体 (T21) 组成型三体的存在是白血病发展的遗传驱动因素，然而，需要额外的致癌突变。因此，T21 提供了更好地了解儿童白血病发生的机会。在这里，我们从体细胞进化的角度描述了儿童期 DS 患白血病的风险增加。根据这个想法，癌症是由细胞群内可遗传表型的变异引起的，这些细胞群在组织环境中受到选择性力的影响。我们提出了一个模型，其中 DS 儿童患白血病的风险增加源于较高的突变积累率，在胎儿发育过程中已经存在，而胎儿肝脏生态位内选择动态的变化进一步增强了突变积累率。该模型可能用于了解生命早期白血病发生的限速步骤。