Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach

• Authors: Nicola Pizzolato , Davide Valenti , Dominique Adorno , Bernardo Spagnolo
• Languages of publication: EN

Abstracts

EN

The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a statistical approach. Cancer progression is explored by applying a Monte Carlo method to simulate the stochastic behavior of cell reproduction and death in a population of blood cells which can experience genetic mutations. In CML front line therapy is represented by the tyrosine kinase inhibitor imatinib which strongly affects the reproduction of leukemic cells only. In this work, we analyze the effects of a targeted therapy on the evolutionary dynamics of normal, first-mutant and cancerous cell populations. Several scenarios of the evolutionary dynamics of imatinib-treated leukemic cells are described as a consequence of the efficacy of the different modelled therapies. We show how the patient response to the therapy changes when a high value of the mutation rate from healthy to cancerous cells is present. Our results are in agreement with clinical observations. Unfortunately, development of resistance to imatinib is observed in a fraction of patients, whose blood cells are characterized by an increasing number of genetic alterations. We find that the occurrence of resistance to the therapy can be related to a progressive increase of deleterious mutations.

Keywords

EN

stochastic dynamics; cancer evolution; complex systems

Discipline

• 87.10.Mn: Stochastic modeling
• 87.10.Rt: Monte Carlo simulations
• 87.19.xj: Cancer
• 87.23.Kg: Dynamics of evolution

• Publisher: De Gruyter Open
• Journal: Open Physics
• Year: 2009
• Volume: 7
• Issue: 3
• Pages: 541-548

Dates

published

1 - 9 - 2009

online

25 - 6 - 2009

Contributors

author

Nicola Pizzolato

author

Davide Valenti

author

Dominique Adorno

• Dipartimento di Fisica e Tecnologie Relative, Università di Palermo and CNISM-INFM, Viale delle Scienze, edificio 18, I-90128, Palermo, Italy

author

Bernardo Spagnolo

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Identifiers

DOI

10.2478/s11534-009-0020-1