2019/07/05 by Tommaso Lorenzi, Lorenzi, Tommaso, Anna Marciniak‐Czochra +3 · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #Chronic Myeloid Leukemia Treatments #Evolution and Genetic Dynamics #Acute Lymphoblastic Leukemia research
paper · pdf · doi:10.48550/arxiv.1907.02842
Recent progress in genetic techniques has shed light on the complex\nco-evolution of malignant cell clones in leukemias. However, several aspects of\nclonal selection still remain unclear. In this paper, we present a\nmulti-compartmental continuously structured population model of selection\ndynamics in acute leukemias, which consists of a system of coupled\nintegro-differential equations. Our model can be analysed in a more efficient\nway than classical models formulated in terms of ordinary differential\nequations. Exploiting the analytical tractability of this model, we investigate\nhow clonal selection is shaped by the self-renewal fraction and the\nproliferation rate of leukemic cells at different maturation stages. We\nintegrate analytical results with numerical solutions of a calibrated version\nof the model based on real patient data. In summary, our mathematical results\nformalise the biological notion that clonal selection is driven by the\nself-renewal fraction of leukemic stem cells and the clones that possess the\nhighest value of this parameter are ultimately selected. Moreover, we\ndemonstrate that the self-renewal fraction and the proliferation rate of\nnon-stem cells do not have a substantial impact on clonal selection. Taken\ntogether, our results indicate that interclonal variability in the self-renewal\nfraction of leukemic stem cells provides the necessary substrate for clonal\nselection to act upon.\n