Cyclical Granulopoiesis in Chronic Granulocytic Leukemia: A Simulation Study

Abstract There exists ample evidence that granulopoiesis is an actively controlled process. The observation of cyclical granulopoiesis in chronic granulocytic leukemia (CGL) suggests that control is deranged rather than abolished in this disorder. Analysis of the kinetics of granulopoiesis in CGL may provide some insight into the nature of the derangement. To facilitate analysis, a mathematical model of the granulopoietic control system is proposed and examined using computer simulation. With model parameters initially chosen to represent normal granulopoiesis, the minimal changes necessary to represent granulopoiesis in CGL were investigated. This analysis indicates that two separate changes seem to be required: (1) the granulocyte maturation time must be increased and (2) the precursor input to the granulocytic pathway of development must also be increased. A causal association between delayed maturation and rising precursor input is suggested, and some possible mechanisms of association are proposed.