Multiplicity of Time Scales in Blood Cell Formation and Leukemia

Abstract

Blood cell formation (hematopoiesis) is a complex and tightly regulated process. It is maintained by hematopoietic (blood-forming) stem cells and serves as a paradigmatic example for tissue maintenance, regeneration, and cancer. Quantitative modeling can provide relevant insights into the dynamics of hematopoiesis in health and disease. This chapter provides an introduction to mechanistic mathematical and computational modeling of blood cell formation and its disorders. Starting with an introduction to the biological background and the concepts of mechanistic modeling a broad spectrum of questions and applications is discussed and illustrated using examples from own previous works. The considerations start with a simple model of white blood cell formation that is stepwisely extended to account for acute myeloid leukemia, one of the most aggressive cancers. The covered aspects range from basic biological questions such as stem cell regulation and interactions in the bone marrow niche to application-driven considerations including bone marrow transplantation, cancer stem cell dynamics, clonal evolution, and blood cancer relapse. The role of mechanistic models for personalized medicine is discussed and illustrated. An important reason for the inherent complexity of hematopoiesis is the fact that it is comprised of a multitude of sub-processes that evolve on different time scales. This chapter provides an overview of the most important sub-processes and their time scales that range from minutes to years. The impact of the different time scales on system dynamics and model development is highlighted.