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System dynamics of cancer in erythropoiesis with multiple EPO feedbacks

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  • Zamra Sajid
  • Morten Andersen
  • Johnny T. Ottesen

Abstract

Blood production is a tightly regulated process, and disturbances can pose a severe risk to human health. Polycythemia vera (PV) is an example of such a disorder characterized by excessive production of erythrocytes and the presence of the JAK2V617F mutation. A 5D PV model with competing healthy and malignant cells, including erythropoietin (EPO), is proposed and analyzed. The production of EPO is governed by the number of erythrocytes, while EPO influences the proliferation and death rate of erythrocytes. Stem cell dynamics can be independently analyzed as a two‐dimensional system. A numerical analysis shows that steady states and their stability of the 2D stem cell PV submodel are in agreement with the PV model. Combining the model with data of PV patients, we demonstrate the model's prognostic significance. It follows that an efficient treatment must target stem cell properties such as the bone marrow microenvironment and stem cell death rates. © 2021 System Dynamics Society

Suggested Citation

  • Zamra Sajid & Morten Andersen & Johnny T. Ottesen, 2020. "System dynamics of cancer in erythropoiesis with multiple EPO feedbacks," System Dynamics Review, System Dynamics Society, vol. 36(4), pages 447-466, October.
    • Handle: RePEc:bla:sysdyn:v:36:y:2020:i:4:p:447-466
    DOI: 10.1002/sdr.1670
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    References listed on IDEAS

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    1. James Rogers & Edward J. Gallaher & David Dingli, 2018. "Personalized ESA doses for anemia management in hemodialysis patients with end‐stage renal disease," System Dynamics Review, System Dynamics Society, vol. 34(1-2), pages 121-153, January.
    2. Özge Karanfil & Yaman Barlas, 2008. "A Dynamic Simulator for the Management of Disorders of the Body Water Homeostasis," Operations Research, INFORMS, vol. 56(6), pages 1474-1492, December.
    3. Thomas Walenda & Thomas Stiehl & Hanna Braun & Julia Fröbel & Anthony D Ho & Thomas Schroeder & Tamme W Goecke & Björn Rath & Ulrich Germing & Anna Marciniak-Czochra & Wolfgang Wagner, 2014. "Feedback Signals in Myelodysplastic Syndromes: Increased Self-Renewal of the Malignant Clone Suppresses Normal Hematopoiesis," PLOS Computational Biology, Public Library of Science, vol. 10(4), pages 1-9, April.
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