A structured population model of clonal selection in acute leukemias with multiple maturation stages

• Verfasst von: Lorenzi, Tommaso [VerfasserIn]
• Verfasst von: Marciniak-Czochra, Anna [VerfasserIn]
• Verfasst von: Stiehl, Thomas [VerfasserIn]
• Titel: A structured population model of clonal selection in acute leukemias with multiple maturation stages
• Verf.angabe: Tommaso Lorenzi, Anna Marciniak-Czochra, Thomas Stiehl
• E-Jahr: 2019
• Jahr: 26 July 2019
• Umfang: 35 S.
• Fussnoten: Gesehen am 12.11.2019
• Titel Quelle: Enthalten in: Journal of mathematical biology
• Ort Quelle: Berlin : Springer, 1974
• Jahr Quelle: 2019
• Band/Heft Quelle: 79(2019), 5, Seite 1587-1621
• ISSN Quelle: 1432-1416
• DOI: doi:10.1007/s00285-019-01404-w
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: 35B40
• Sach-SW: 35Q92
• Sach-SW: 35R09
• Sach-SW: Acute leukemia
• Sach-SW: Asymptotic analysis
• Sach-SW: Clonal selection
• Sach-SW: Continuously structured population models
• Sach-SW: Integro-differential equations
• K10plus-PPN: 1681676109

Abstract

Recent progress in genetic techniques has shed light on the complex co-evolution of malignant cell clones in leukemias. However, several aspects of clonal selection still remain unclear. In this paper, we present a multi-compartmental continuously structured population model of selection dynamics in acute leukemias, which consists of a system of coupled integro-differential equations. Our model can be analysed in a more efficient way than classical models formulated in terms of ordinary differential equations. Exploiting the analytical tractability of this model, we investigate how clonal selection is shaped by the self-renewal fraction and the proliferation rate of leukemic cells at different maturation stages. We integrate analytical results with numerical solutions of a calibrated version of the model based on real patient data. In summary, our mathematical results formalise the biological notion that clonal selection is driven by the self-renewal fraction of leukemic stem cells and the clones that possess the highest value of this parameter are ultimately selected. Moreover, we demonstrate that the self-renewal fraction and the proliferation rate of non-stem cells do not have a substantial impact on clonal selection. Taken together, our results indicate that interclonal variability in the self-renewal fraction of leukemic stem cells provides the necessary substrate for clonal selection to act upon.