Oscillations in cyclical neutropenia:: new evidence based on mathematical modeling

We present a dynamical model of the production and regulation of circulating blood neutrophil number. This model is derived from physiologically relevant features of the hematopoietic system, and is analysed using both analytic and numerical methods. Supercritical Hopf bifurcations and saddle-node bifurcations of limit cycles are shown to exist. We make the estimation of kinetic parameters for dogs and then apply the model to cyclical neutropenia (CN) in the grey collie, a rare disorder in which oscillations in all blood cell counts are found. We conclude that the major cause of the oscillations in CN is an increased rate of apoptosis of neutrophil precursors which leads to a destabilization of the hematopoietic stem cell compartment. (C) 2003 Elsevier Ltd. All rights reserved.