ArticleJournal of theoretical biology2016
Feedback mechanisms control coexistence in a stem cell model of acute myeloid leukaemia.
Article in Journal of theoretical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 27 citations in OpenAlex.
- Optimal control of multiple myeloma assuming drug resistance and off-target effects.PLoS computational biology · 2025Article
- Predictive nonlinear modeling of malignant myelopoiesis and tyrosine kinase inhibitor therapy.eLife · 2023Article
- Implementation and acceleration of optimal control for systems biology.Journal of the Royal Society, Interface · 2021Review
- Differential response to cytotoxic therapy explains treatment dynamics of acute myeloid leukaemia patients: insights from a mathematical modelling approach.Journal of the Royal Society, Interface · 2020Article
- Clonal hematopoiesis of indeterminate potential and its impact on patient trajectories after stem cell transplantation.PLoS computational biology · 2019Article
- Study of cohabitation and interconnection effects on normal and leukaemic stem cells dynamics in acute myeloid leukaemia.IET systems biology · 2018Article
- Feedback regulation in a stem cell model with acute myeloid leukaemia.BMC systems biology · 2018Article
- The proportion of cancer-related entries in PubMed has increased considerably; is cancer truly "The Emperor of All Maladies"?PloS one · 2017Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Haematopoietic stem cell dynamics regulate healthy blood cell production and are disrupted during leukaemia. Competition models of cellular species help to elucidate stem cell dynamics in the bone marrow microenvironment (or niche), and to determine how these dynamics impact leukaemia progression. Here we develop two models that target acute myeloid leukaemia with particular focus on the mechanisms that control proliferation via feedback signalling. It is within regions of parameter space permissive of coexistence that the effects of competition are most subtle and the clinical outcome least certain. Steady state and linear stability analyses identify parameter regions that allow for coexistence to occur, and allow us to characterise behaviour near critical points. Where analytical expressions are no longer informative, we proceed statistically and sample parameter space over a coexistence region. We find that the rates of proliferation and differentiation of healthy progenitors exert key control over coexistence. We also show that inclusion of a regulatory feedback onto progenitor cells promotes healthy haematopoiesis at the expense of leukaemia, and that - somewhat paradoxically - within the coexistence region feedback increases the sensitivity of the system to dominance by one lineage over another.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.