伊马替尼对白血病细胞演化动力学的随机模拟
Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach
摘要：
用统计方法研究了慢性粒细胞白血病（CML）模型中癌细胞系统的演化动力学。通过应用蒙特卡罗方法模拟可能经历基因突变的血细胞群体中细胞繁殖和死亡的随机行为来探索癌症进展。在CML中，一线治疗以酪氨酸激酶抑制剂伊马替尼为代表，其仅强烈影响白血病细胞的繁殖。在这项工作中，我们分析了靶向治疗对正常，第一突变和癌细胞群体的演化动力学的影响。伊马替尼治疗的白血病细胞的演化动力学的几种情况被描述为不同建模疗法的疗效的结果。我们展示了当从健康细胞到癌细胞的突变率值很高时，患者对治疗的反应是如何变化的。我们的结果与临床观察一致。不幸的是，在一定比例的患者中观察到对伊马替尼的耐药性的发展，其血细胞的特征在于越来越多的遗传改变。我们发现，对治疗的耐药性的发生可能与有害突变的逐步增加有关。
英文摘要：
The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a statistical approach. Cancer progression is explored by applying a Monte Carlo method to simulate the stochastic behavior of cell reproduction and death in a population of blood cells which can experience genetic mutations. In CML front line therapy is represented by the tyrosine kinase inhibitor imatinib which strongly affects the reproduction of leukemic cells only. In this work, we analyze the effects of a targeted therapy on the evolutionary dynamics of normal, first-mutant and cancerous cell populations. Several scenarios of the evolutionary dynamics of imatinib-treated leukemic cells are described as a consequence of the efficacy of the different modeled therapies. We show how the patient response to the therapy changes when an high value of the mutation rate from healthy to cancerous cells is present. Our results are in agreement with clinical observations. Unfortunately, development of resistance to imatinib is observed in a proportion of patients, whose blood cells are characterized by an increasing number of genetic alterations. We find that the occurrence of resistance to the therapy can be related to a progressive increase of deleterious mutations.
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