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

Tommaso Lorenzi, Anna Marciniak-Czochra, Thomas Stiehl

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.
Original languageEnglish
Number of pages35
JournalJournal of Mathematical Biology
VolumeFirst Online
Early online date26 Jul 2019
DOIs
Publication statusE-pub ahead of print - 26 Jul 2019

Keywords

  • Acute Leukemia
  • Clonal selection
  • Continuously structured population models
  • Integro-differential equations
  • Asymptotic analysis

Fingerprint

Dive into the research topics of 'A structured population model of clonal selection in acute leukemias with multiple maturation stages'. Together they form a unique fingerprint.

Cite this