Jan-Erik Busse | Searcharxiv

arXiv2020

Local asymptotic stability of a system of integro-differential equations describing clonal evolution of a self-renewing cell population under mutation

In this paper we consider a system of non-linear integro-differential equations (IDEs) describing evolution of a clonally heterogeneous population of malignant white blood cells (leukemic cells) undergoing mutation and clonal selection. We prove existence and uniqueness of non-trivial steady states and study their asymptotic stability. The results are compared to those of the system without mutation. Existence of equilibria is proved by formulating the steady state problem as an eigenvalue problem and applying a version of the Krein-Rutmann theorem for Banach lattices. The stability at equilibrium is analysed using linearisation and the Weinstein-Aronszajn determinant which allows to conclude local asymptotic stability.

math.DS↗

arXiv2016

Mass concentration in a nonlocal model of clonal selection

Self-renewal is a constitutive property of stem cells. Testing the cancer stem cell hypothesis requires investigation of the impact of self-renewal on cancer expansion. To understand better this impact, we propose a mathematical model describing dynamics of a continuum of cell clones structured by the self-renewal potential. The model is an extension of the finite multi-compartment models of interactions between normal and cancer cells in acute leukemias. It takes a form of a system of integro-differential equations with a nonlinear and nonlocal coupling, which describes regulatory feedback loops in cell proliferation and differentiation process. We show that such coupling leads to mass concentration in points corresponding to maximum of the self-renewal potential and the model solutions tend asymptotically to a linear combination of Dirac measures. Furthermore, using a Lyapunov function constructed for a finite dimensional counterpart of the model, we prove that the total mass of the solution converges to a globally stable equilibrium. Additionally, we show stability of the model in space of positive Radon measures equipped with flat metric. The analytical results are illustrated by numerical simulations.

math.CA↗