论文标题
使用三阶段随机模型研究发作年龄和检测慢性髓样白血病的年龄
Studying the age of onset and detection of Chronic Myeloid Leukemia using a three-stage stochastic model
论文作者
论文摘要
慢性髓样白血病（CML）是一种双相恶性克隆疾病，首先以慢性相进行，其中细胞仅增强增殖，然后在爆炸阶段，在爆炸阶段，在该阶段，细胞具有自我更新的能力。众所周知，费城染色体（包含BCR-ABL融合基因）是“ CML的标志”。但是，经验研究表明，仅BCR-ABL的存在可能不是CML发展的足够条件，并且可能需要与肿瘤抑制器有关的进一步修改。因此，我们开发了CML进展的三个伴随的随机模型，三个阶段对应于具有BCR-ABL存在的非恶性细胞，在慢性相中的恶性细胞和在爆炸阶段的恶性细胞。我们证明，模型预测与美国的年龄发病率数据一致。最后，我们开发了一个框架，用于从检测到癌症时对恶性肿瘤发作时间进行回顾性估计。
Chronic Myeloid Leukemia (CML) is a biphasic malignant clonal disorder that progresses, first with a chronic phase, where the cells have enhanced proliferation only, and then to a blast phase, where the cells have the ability of self-renewal. It is well-recognized that the Philadelphia chromosome (which contains the BCR-ABL fusion gene) is the "hallmark of CML". However, empirical studies have shown that the mere presence of BCR-ABL may not be a sufficient condition for the development of CML, and further modifications related to tumor suppressors may be necessary. Accordingly, we develop a three-mutation stochastic model of CML progression, with the three stages corresponding to the non-malignant cells with BCR-ABL presence, the malignant cells in the chronic phase and the malignant cells in the blast phase. We demonstrate that the model predictions agree with age incidence data from the United States. Finally, we develop a framework for the retrospective estimation of the time of onset of malignancy, from the time of detection of the cancer.
