Dynamics of competing heterogeneous clones in blood cancers explains multiple observations - a mathematical modeling approach

Katrine O. Bangsgaard, Morten Wienecke Andersen, Vibe Skov, Lasse Kjær, Hans Hasselbalch, Johnny T. Ottesen*

*Corresponding author

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Heterogeneity of stem cell clones provide a key ingredient in altered hematopoiesis and is of main interest in the study of predisease states as well as in the development of blood cancers such as chronic myeloid leukemia (CML) and the Philadelphia-negative myeloprofilerative neoplasms (MPNs). A mathematical model based on biological mechanisms and basic cell descriptors such as proliferation rates and apoptosis rates is suggested, connecting stem cell dynamics with mature blood cells and immune mediated feedback. The flexible approach allows for arbitrary numbers of mutated stem cell clones with perturbed properties. In particular, the stem cell niche provides a competition between wild type and mutated stem cells. Hence, the stem cell niche can mediate suppression of the wild type clones and up-regulation of one or more malignant clones. The model is parameterized using clinical data to show typical disease progression in several blood cancers and the hematological and molecular response to treatment. Intriguingly, occasional oscillatory cell counts observed during treatment of CML and MPNs can be explained by heterogeneous stem cell clone dynamics. Thus, the vital heterogeneous stem cell dynamics may be inferred from mathematical modeling in synergy with clinical data to elucidate hematopoiesis, blood cancers and the outcome of interventions.
Original languageEnglish
JournalMathematical Biosciences and Engineering
Volume17
Issue number6
Pages (from-to)7645-7670
Number of pages26
ISSN1547-1063
DOIs
Publication statusPublished - 2020

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