几乎所有癌症类型都有癌症的标志和类似的肿瘤形成方式：由体细胞内的随机突变产生。针对慢性髓系白血病（CML），这个演化过程可从无症状的慢性期追溯到最终的快速进展期。CML的体细胞演化发生在健康的血液生成环境中，这是一个细胞分裂的层次过程；由自我更新和分化产生成熟血细胞的干细胞发起。在这里，我们介绍了一个分层细胞分裂的通用模型，解释了CML的特定进展，结果来自于造血系统的结构。驱动突变为携带它们的细胞提供生长优势，例如，BCR :: ABL1基因，它也作为CML的标志。我们通过使用计算机模拟和将模型参数适应于慢性和加速期中报道的中位数持续时间来研究BCR :: ABL1突变强度与造血干细胞分化速率的关系。我们的结果表明，如果干细胞分裂足够缓慢，则必须添加驱动突变（另外还有BCR :: ABL1突变）来解释CML的进展。我们观察到，在细胞分化层次结构的更高级别上积累的突变数不受存在于干细胞中的驱动突变的影响。我们的结果揭示了分层组织中的体细胞演化，并显示CML进展的临床标志是由血液生成的结构特征产生的。 ©2023.作者。

Almost all cancer types share the hallmarks of cancer and a similar tumor formation: fueled by stochastic mutations in somatic cells. In case of chronic myeloid leukemia (CML), this evolutionary process can be tracked from an asymptomatic long-lasting chronic phase to a final rapidly evolving blast phase. Somatic evolution in CML occurs in the context of healthy blood production, a hierarchical process of cell division; initiated by stem cells that self-renew and differentiate to produce mature blood cells. Here we introduce a general model of hierarchical cell division explaining the particular progression of CML as resulting from the structure of the hematopoietic system. Driver mutations confer a growth advantage to the cells carrying them, for instance, the BCR::ABL1 gene, which also acts as a marker for CML. We investigated the relation of the BCR::ABL1 mutation strength to the hematopoietic stem cell division rate by employing computer simulations and fitting the model parameters to the reported median duration for the chronic and accelerated phases. Our results demonstrate that driver mutations (additional to the BCR::ABL1 mutation) are necessary to explain CML progression if stem cells divide sufficiently slowly. We observed that the number of mutations accumulated by cells at the more differentiated levels of the hierarchy is not affected by driver mutations present in the stem cells. Our results shed light on somatic evolution in a hierarchical tissue and show that the clinical hallmarks of CML progression result from the structural characteristics of blood production.© 2023. The Author(s).