Population dynamics of normal and leukaemia stem cells in the haematopoietic stem cell niche show distinct regimes where leukaemia will be controlled

Haematopoietic stem cells (HSCs) are responsible for maintaining immune cells, red blood cells and platelets throughout life. HSCs must be located in their ecological niche (the bone marrow) to function correctly, that is, to regenerate themselves and their progeny; the latter eventually exit the bo...

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Autores principales: MacLean, Adam L., Lo Celso, Cristina, Stumpf, Michael P. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627104/
https://www.ncbi.nlm.nih.gov/pubmed/23349436
http://dx.doi.org/10.1098/rsif.2012.0968
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author MacLean, Adam L.
Lo Celso, Cristina
Stumpf, Michael P. H.
author_facet MacLean, Adam L.
Lo Celso, Cristina
Stumpf, Michael P. H.
author_sort MacLean, Adam L.
collection PubMed
description Haematopoietic stem cells (HSCs) are responsible for maintaining immune cells, red blood cells and platelets throughout life. HSCs must be located in their ecological niche (the bone marrow) to function correctly, that is, to regenerate themselves and their progeny; the latter eventually exit the bone marrow and enter circulation. We propose that cells with oncogenic potential—cancer/leukaemia stem cells (LSC)—and their progeny will also occupy this niche. Mathematical models, which describe the dynamics of HSCs, LSCs and their progeny allow investigation into the conditions necessary for defeating a malignant invasion of the niche. Two such models are developed and analysed here. To characterize their behaviour, we use an inferential framework that allows us to study regions in parameter space that give rise to desired behaviour together with an assessment of the robustness of the dynamics. Using this approach, we map out conditions under which HSCs can outcompete LSCs. In therapeutic applications, we clearly want to drive haematopoiesis into such regimes and the current analysis provide some guidance as to how we can identify new therapeutic targets. Our results suggest that maintaining a viable population of HSCs and their progenies in the niche may often already be nearly sufficient to eradicate LSCs from the system.
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spelling pubmed-36271042013-05-01 Population dynamics of normal and leukaemia stem cells in the haematopoietic stem cell niche show distinct regimes where leukaemia will be controlled MacLean, Adam L. Lo Celso, Cristina Stumpf, Michael P. H. J R Soc Interface Research Articles Haematopoietic stem cells (HSCs) are responsible for maintaining immune cells, red blood cells and platelets throughout life. HSCs must be located in their ecological niche (the bone marrow) to function correctly, that is, to regenerate themselves and their progeny; the latter eventually exit the bone marrow and enter circulation. We propose that cells with oncogenic potential—cancer/leukaemia stem cells (LSC)—and their progeny will also occupy this niche. Mathematical models, which describe the dynamics of HSCs, LSCs and their progeny allow investigation into the conditions necessary for defeating a malignant invasion of the niche. Two such models are developed and analysed here. To characterize their behaviour, we use an inferential framework that allows us to study regions in parameter space that give rise to desired behaviour together with an assessment of the robustness of the dynamics. Using this approach, we map out conditions under which HSCs can outcompete LSCs. In therapeutic applications, we clearly want to drive haematopoiesis into such regimes and the current analysis provide some guidance as to how we can identify new therapeutic targets. Our results suggest that maintaining a viable population of HSCs and their progenies in the niche may often already be nearly sufficient to eradicate LSCs from the system. The Royal Society 2013-04-06 /pmc/articles/PMC3627104/ /pubmed/23349436 http://dx.doi.org/10.1098/rsif.2012.0968 Text en http://creativecommons.org/licenses/by/3.0/ © 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research Articles
MacLean, Adam L.
Lo Celso, Cristina
Stumpf, Michael P. H.
Population dynamics of normal and leukaemia stem cells in the haematopoietic stem cell niche show distinct regimes where leukaemia will be controlled
title Population dynamics of normal and leukaemia stem cells in the haematopoietic stem cell niche show distinct regimes where leukaemia will be controlled
title_full Population dynamics of normal and leukaemia stem cells in the haematopoietic stem cell niche show distinct regimes where leukaemia will be controlled
title_fullStr Population dynamics of normal and leukaemia stem cells in the haematopoietic stem cell niche show distinct regimes where leukaemia will be controlled
title_full_unstemmed Population dynamics of normal and leukaemia stem cells in the haematopoietic stem cell niche show distinct regimes where leukaemia will be controlled
title_short Population dynamics of normal and leukaemia stem cells in the haematopoietic stem cell niche show distinct regimes where leukaemia will be controlled
title_sort population dynamics of normal and leukaemia stem cells in the haematopoietic stem cell niche show distinct regimes where leukaemia will be controlled
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627104/
https://www.ncbi.nlm.nih.gov/pubmed/23349436
http://dx.doi.org/10.1098/rsif.2012.0968
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