Speaker
Description
Myeloproliferative neoplasms (MPN) are a group of hematological malignancies characterized by an overproduction of myeloid blood cells. A recent mathematical model (\cite{B}) coupling hematopoiesis, inflammation, MPN progression and treatment inhibiting inflammation is here analyzed from a dynamical systems perspective.
The model includes time varying populations of stem cells, progenitor cells, mature blood cells and their mutated counterparts, cellular debris, and inflammatory feedback resulting in an eight dimensional, nonlinear ode-model.
A compact, positively invariant subset of the phase space is found, guaranteeing trajectories exist for all forward time (no blow up, even in the case of malignant cells).
The problem of identifying steady states is greatly simplified, by derivation of a low order polynomial (at most 4th order) in a single variable, providing analytical upper bounds on healthy, malignant and coexistence steady states and ensure a fast algorithm to describe all steady states for a given set of parameter values.
Critical parameter values related to treatment of various type acting on stem cell, progenitor cell and inflammatory feedback is then varied, resulting in more than $10^6$ cases to be analyzed. 13 different flow patterns are observed and categorized, and the effects of perturbing several parameters at a time are summarized in bifurcation diagrams providing a theoretical test bed for potential treatment, including combination of several drugs.
Bibliography
@ARTICLE{B,
AUTHOR={Boklund, Tobias Idor and Snyder, Jordan and Gudmand-Hoeyer, Johanne and Larsen, Morten Kranker and Knudsen, Trine Alma and Eickhardt-Dalbøge, Christina Schjellerup and Skov, Vibe and Kjær, Lasse and Hasselbalch, Hans C. and Andersen, Morten and Ottesen, Johnny T. and Stiehl, Thomas },
TITLE={Mathematical modelling of stem and progenitor cell dynamics during ruxolitinib treatment of patients with myeloproliferative neoplasms},
JOURNAL={Frontiers in Immunology},
VOLUME={Volume 15 - 2024},
YEAR={2024},
URL={https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1384509},
DOI={10.3389/fimmu.2024.1384509},
ISSN={1664-3224},
}
