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Modeling Imatinib-Treated Chronic Myelogenous Leukemia: Reducing the Complexity of Agent-Based Models

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Abstract

We develop a model for describing the dynamics of imatinib-treated chronic myelogenous leukemia. Our model is based on replacing the recent agent-based model of Roeder et al. (Nat. Med. 12(10):1181–1184, 2006) by a system of deterministic difference equations. These difference equations describe the time-evolution of clusters of individual agents that are grouped by discretizing the state space. Hence, unlike standard agent-base models, the complexity of our model is independent of the number of agents, which allows to conduct simulation studies with a realistic number of cells. This approach also allows to directly evaluate the expected steady states of the system. The results of our numerical simulations show that our model replicates the averaged behavior of the original Roeder model with a significantly reduced computational cost. Our general approach can be used to simplify other similar agent-based models. In particular, due to the reduced computational complexity of our technique, one can use it to conduct sensitivity studies of the parameters in large agent-based systems.

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References

  • Bernard, S., Belair, J., Mackey, M.C., 2003. Oscillations in cyclical neutropenia: new evidence based on mathematical modeling. J. Theor. Biol. 223(3), 283–298.

    Article  MathSciNet  Google Scholar 

  • Campbell, J.D., Cook, G., Holyoake, T.L., 2001. Evolution of bone marrow transplantation—the original immunotherapy. Trends Immunol. 22(2), 88–92.

    Article  Google Scholar 

  • Druker, B.J., Lydon, N.B., 2000. Lessons learned from the development of an ABL tyrosine kinase inhibitor for chronic myelogenous leukemia. J. Clin. Invest. 105(1), 3–7.

    Article  Google Scholar 

  • Fokas, A.S., Keller, J.B., Clarkson, B.D., 1991. Mathematical model of granulocytopoiesis and chronic myelogenous leukemia. Cancer Res. 51(8), 2084–2091.

    Google Scholar 

  • Komarova, N.L., Wodarz, D., 2005. Drug resistance in cancer: principles of emergence and prevention. Proc. Natl. Acad. Sci. USA 102(27), 9714–9719.

    Article  Google Scholar 

  • Michor, F., Hughes, T.P., Iwasa, Y., Branford, S., Shah, N.P., Sawyers, C.L., Nowak, M.A., 2005. Dynamics of chronic myeloid leukemia. Nature 435(7046), 1267–1270.

    Article  Google Scholar 

  • Moore, H., Li, N.K., 2004. A mathematical model for chronic myelogenous leukemia (CML) and T cell interaction. J. Theor. Biol. 225(4), 513–523.

    Article  MathSciNet  Google Scholar 

  • Neiman, B., 2002. A mathematical model of chronic myelogenous leukemia. Master’s thesis, University College, Oxford University, UK.

  • Roeder, I., 2003. Dynamical modeling of hematopoietic stem cell organization—design and validation of the new concept of within-tissue plasticity. PhD thesis, University of Leipzig, Germany.

  • Roeder, I., Horn, M., Glauche, I., Hochhaus, A., Mueller, M.C., Loeffler, M., 2006. Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional insights and clinical implications. Nat. Med. 12(10), 1181–1184.

    Article  Google Scholar 

  • Rubinow, S.I., Lebowitz, J.L., 1976a. A mathematical model of the acute myeloblastic leukemic state in man. Biophys. J. 16(8), 897–910.

    Google Scholar 

  • Rubinow, S.I., Lebowitz, J.L., 1976b. A mathematical model of the chemotherapeutic treatment of acute myeloblastic leukemia. Biophys. J. 16(11), 1257–1271.

    Article  Google Scholar 

  • Rubinow, S.I., Lebowitz, J.L., 1977. A mathematical model of the acute myeloblastic leukemic state in man. Biosystems 8(4), 265–266.

    Article  Google Scholar 

  • Thijsen, S.F.T., Schuurhuis, G.J., van Oostveen, J.W., Ossenkoppele, G.J., 1999. Chronic mlyeloid leukemia from basics to bedside. Leukemia 13(11), 1646–1674.

    Article  Google Scholar 

  • Vincent, P.C., Cronkite, E.P., Greenberg, M.L., Kirsten, C., Schiffer, L.M., Stryckmans, P.A., 1969. Leukocyte kinetics in chronic myeloid leukemia. I. DNA synthesis time in blood and marrow myelocytes. Blood 33(6), 843–850.

    Google Scholar 

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Correspondence to Doron Levy.

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Kim, P.S., Lee, P.P. & Levy, D. Modeling Imatinib-Treated Chronic Myelogenous Leukemia: Reducing the Complexity of Agent-Based Models. Bull. Math. Biol. 70, 728–744 (2008). https://doi.org/10.1007/s11538-007-9276-z

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  • DOI: https://doi.org/10.1007/s11538-007-9276-z

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