Blood production is a tightly regulated process, and disturbances can pose a severe risk to human health. Polycythemia vera (PV) is an example of such a disorder characterized by excessive production of erythrocytes and the presence of the JAK2V617F mutation. A 5D PV model with competing healthy and malignant cells, including erythropoietin (EPO), is proposed and analyzed. The production of EPO is governed by the number of erythrocytes, while EPO influences the proliferation and death rate of erythrocytes. Stem cell dynamics can be independently analyzed as a two‐dimensional system. A numerical analysis shows that steady states and their stability of the 2D stem cell PV submodel are in agreement with the PV model. Combining the model with data of PV patients, we demonstrate the model's prognostic significance. It follows that an efficient treatment must target stem cell properties such as the bone marrow microenvironment and stem cell death rates. © 2021 System Dynamics Society

中文翻译：

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具有多个EPO反馈的红细胞生成中癌症的系统动力学

血液生产是严格控制的过程，干扰可能对人类健康构成严重威胁。真性红细胞增多症（PV）是这种疾病的一个例子，其特征是红血球过多产生和JAK2的存在V617F突变。提出并分析了具有竞争性健康和恶性细胞（包括促红细胞生成素（EPO））的5D PV模型。EPO的产生取决于红细胞的数量，而EPO影响红细胞的增殖和死亡率。干细胞动力学可以作为二维系统进行独立分析。数值分析表明，二维干细胞PV子模型的稳态及其稳定性与PV模型一致。将模型与PV患者的数据相结合，我们证明了该模型的预后意义。因此，有效的治疗必须针对干细胞特性，例如骨髓微环境和干细胞死亡率。©2021系统动力学学会