A structured population model of clonal selection in acute leukemias with multiple maturation stages
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...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
26 July 2019
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| In: |
Journal of mathematical biology
Year: 2019, Volume: 79, Issue: 5, Pages: 1587-1621 |
| ISSN: | 1432-1416 |
| DOI: | 10.1007/s00285-019-01404-w |
| Online Access: | Verlag, Volltext: https://doi.org/10.1007/s00285-019-01404-w
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| Author Notes: | Tommaso Lorenzi, Anna Marciniak-Czochra, Thomas Stiehl |
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| 520 | |a 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. | ||
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