A mathematical model of hematopolesis: II. Cyclical neutropenia
A mathematical model of hematopolesis: II. Cyclical neutropenia
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DOI：
10.1016/j.jtbi.2005.03.034
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发表时间：
2005-11-21
影响因子：
2
通讯作者：
Mackey, MC
中科院分区：
文献类型：
--
作者：
Colijn, C;Mackey, MC
周期性中性粒细胞减少症是造血系统的动力学疾病，其特征在于循环白细胞（例如中性粒细胞）数量振荡至接近零水平，然后恢复正常。这种振荡也反映在血小板和网织红细胞中，它们以相同的周期振荡。周期性中性粒细胞减少症在灰色牧羊犬中有动物对应物。本文利用Colijn和Mackey的造血系统数学模型[造血系统的数学模型：I.周期性慢性粒细胞白血病。本文件的配套文件]。我们已经确定了模拟未治疗的灰色牧羊犬和人类的实验室和临床数据所需的参数，以及在用粒细胞集落刺激因子（G-CSF）治疗期间拟合数据所需的这些参数的变化。与正常稳态值相比。我们发现，模拟未治疗的周期性中性粒细胞减少症的主要参数变化对应于增殖的中性粒细胞前体区室内扩增减少（凋亡增加），以及重新进入干细胞区室增殖期的最大速率降低。对于在G-CSF处理期间获得的数据，仅当参数改变时才获得良好的拟合，这意味着G-CSF导致增殖的中性粒细胞前体中的较高扩增（较低的凋亡率）。以及向中性粒细胞系的分化率升高。(c)2005爱思唯尔有限公司保留所有权利。
Cyclical neutropenia is a dynamical disease of the hematopoietic system marked by an oscillation in circulating leukocyte (e.g. neutrophil) numbers to near zero levels and then back to normal. This oscillation is also mirrored in the platelets and reticulocytes which oscillate with the same period. Cyclical neutropenia has an animal counterpart in the grey collie. Using the mathematical model of the hematopoietic system of Colijn and Mackey [A mathematical model of hematopoiesis: I. Periodic chronic myelogenous leukemia. Companion paper to the present paper.] we have determined what parameters are necessary to mimic laboratory and clinical data on untreated grey collies and humans, and also what changes in these parameters are necessary to fit data during treatment with granulocyte colony stimulating factor (G-CSF). Compared to the normal steady-state values. we found that the major parameter changes that mimic untreated cyclical neutropenia correspond to a decreased amplification (increased apoptosis) within the proliferating neutrophil precursor compartment, and a decrease in the maximal rate of re-entry into the proliferative phase of the stem cell compartment. For the data obtained during G-CSF treatment, good fits were obtained only when parameters were altered that would imply that G-CSF led to higher amplification (lower rate of apoptosis) in the proliferating neutrophil precursors. and a elevated rate of differentiation into the neutrophil line. (c) 2005 Elsevier Ltd. All rights reserved.