Mathematical modeling of multiple myeloma intraclonal heterogeneity, drug resistance, and impact on erythropoiesis

Multiple myeloma (MM) is a highly complex, heterogeneous and evolving hematological disease. Patients with MM often harbor between three to seven subclones that have a variety of mutations, which poses a challenge to the success of chemotherapy. Myeloma infiltration to the bone marrow affects the balance of erythropoiesis which causes reversible anemia. In this work, we will review some of our modeling studies devoted to MM heterogeneity, drug resistance, and impact on erythropoiesis. In this talk, we will introduce the biological background, clinical presentation, and treatment options for this disease. Next, we will describe two methods which we have developed to describe MM intraclonal heterogeneity. The first consists in using a multiscale model that describes cells explicitly, while the second is a phenotype-structured model which accounts for the evolutionary forces affecting the progression of the pathology. Next, we will see how modeling can be used to design therapeutic strategies that overcome MM resistance to tyrosine kinase inhibitors. Finally, we will study the impact of MM infiltration on erythropoiesis and anemia. We will conclude this talk by discussing some perspectives and challenges in MM modeling.