Speaker
Description
We present the Multiple Clone Cancitis (MCC) model describing the blood
cancers AML, CML, and MPNs despite its differences [1]. The MCC model is
based on biological mechanisms, basic cell descriptors such as proliferation rates,
and apoptosis rates connecting stem cell dynamics with mature blood cells and
immune mediated feedback including an explicitly cytotoxic T-cell mediated
death of malignant stem cells.
The unifying and flexible MCC model approach allows for arbitrary numbers
of mutated stem cell clones with perturbed properties. The stem cell niche
mediate suppression of the wild type clones due to resources restrictions etc.
and the microenvironment may cause the cytotoxic T-cell to have different death
rates in killing malignant stem cells and stem cell like progenitors.
The unifying MCC model comprehensively explains,
• Patient data
• Frequently observed oscillations in cell count of time scale 2–3 months for
hydroxyurea treated CML patients.
• Less frequently observed oscillations in cell count of time scale 1 month
for hydroxyurea treated MPN patients.
• Consequences of CHIP leading to good, fair, poor, or vital responders to
treatment.
• Elimination, equilibrium, and escape phases related to immunoediting.
• Developed of immune resistance to treatment.
• The evolution of clones over the life span of a human.
Bibliography
Katrine O. Bangsgaard, Morten Andersen, Vibe Skov, Lasse Kjær, Hans C.
Hasselbalch, and Johnny T. Ottesen (2020) Dynamics of competing heterogeneous
clones in blood cancers explains multiple observations - a mathematical
modeling approach. Mathematical Biosciences and Engineering (MBE),
17(6): 7645–7670. DOI: 10.3934/mbe.2020389
