A Mathematical Model of Clonal Hematopoiesis Explaining Phase Transitions in Chronic Myeloid Leukemia.

Abstract

This study presents a mathematical model describing cloned hematopoiesis in chronic myeloid leukemia (CML) through a nonlinear system of differential equations. The primary objective is to understand the progression from healthy hematopoiesis to the chronic and accelerated-acute phases in myeloid leukemia. The model incorporates intrinsic cellular division events in hematopoiesis and delineates the evolution of chronic myeloid leukemia into five compartments: cycling stem cells, quiescent stem cells, progenitor cells, differentiated cells, and terminally differentiated cells. Our analysis reveals the existence of three distinct non-zero steady states within the dynamical system, representing healthy hematopoiesis, the chronic phase, and the accelerated-acute stage of the disease. We investigate the local and global stability of these steady states and provide a characterization of the hematopoietic states based on this analysis. Additionally, numerical simulations are included to illustrate the theoretical results.