2017/07/31 by Peter Ashcroft, Markus G. Manz, Sebastian Bonhoeffer · 37 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Acute Myeloid Leukemia Research #Biology #Bone marrow #Cell biology #Computational biology #Dominance (genetics) #Gene #Genetics #Haematopoiesis #Hematopoietic Stem Cell Transplantation #Hematopoietic stem cell #Hematopoietic stem cell transplantation #Immunology #Internal medicine #Medicine #Myeloproliferative Neoplasms: Diagnosis and Treatment #Stem cell #Transplantation #q-bio.PE
paper · pdf · doi:10.1371/journal.pcbi.1005803
published in PLoS Computational Biology 13(10), e1005803 (Public Library of Science) · 46 pages, 11 figures (inclusive of SI)
openalex publication_date 2017/10/09 · arxiv created 2017/10/11 · arxiv updated 2017/10/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
Hematopoietic stem cells in mammals are known to reside mostly in the bone marrow, but also transitively passage in small numbers in the blood. Experimental findings have suggested that they exist in a dynamic equilibrium, continuously migrating between these two compartments. Here we construct an individual-based mathematical model of this process, which is parametrised using existing empirical findings from mice. This approach allows us to quantify the amount of migration between the bone marrow niches and the peripheral blood. We use this model to investigate clonal hematopoiesis, which is a significant risk factor for hematologic cancers. We also analyse the engraftment of donor stem cells into non-conditioned and conditioned hosts, quantifying the impact of different treatment scenarios. The simplicity of the model permits a thorough mathematical analysis, providing deeper insights into the dynamics of both the model and of the real-world system. We predict the time taken for mutant clones to expand within a host, as well as chimerism levels that can be expected following transplantation therapy, and the probability that a preconditioned host is reconstituted by donor cells.