Stochastic Hypothesis of Transition from Inborn Neutropenia to AML: Interactions of Cell Population Dynamics and Population Genetics.
Stochastic Hypothesis of Transition from Inborn Neutropenia to AML: Interactions of Cell Population Dynamics and Population Genetics.
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DOI：
10.3389/fonc.2013.00089
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发表时间：
2013
影响因子：
4.7
通讯作者：
Corey S
中科院分区：
文献类型：
--
作者：
Kimmel M;Corey S
我们提出了一个随机模型的驱动突变的过渡，从严重的先天性中性粒细胞减少症骨髓增生异常综合征急性髓细胞白血病（AML）。该模型具有多类型分支过程的形式。我们推导出连续驱动突变的时间分布方程，并建立了涉及一系列假设的模拟，这些假设涉及连续突变克隆中突变率的加速。我们的模型再现了继发性AML诊断时间的临床分布。令人惊讶的是，在我们的假设框架内，突变过程的随机性无法解释在这种情况下诊断AML时的时间分布;有必要另外假设疾病病例中增殖参数的广泛分布。这一发现出乎意料，但通常与人类癌症特征的广泛异质性一致。
We present a stochastic model of driver mutations in the transition from severe congenital neutropenia to myelodysplastic syndrome to acute myeloid leukemia (AML). The model has the form of a multitype branching process. We derive equations for the distributions of the times to consecutive driver mutations and set up simulations involving a range of hypotheses regarding acceleration of the mutation rates in successive mutant clones. Our model reproduces the clinical distribution of times at diagnosis of secondary AML. Surprisingly, within the framework of our assumptions, stochasticity of the mutation process is incapable of explaining the spread of times at diagnosis of AML in this case; it is necessary to additionally assume a wide spread of proliferative parameters among disease cases. This finding is unexpected but generally consistent with the wide heterogeneity of characteristics of human cancers.