Clonal Dominance and Transplantation Dynamics in Hematopoietic Stem Cell Compartments
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.
Code (1)
Similar Papers 제목 키워드 기반
A Dynamical Systems Perspective on Chimeric Antigen Receptor T-Cell Dosing
Chimeric antigen receptor T cells (CAR T cells) are dosed similarly to donor lymphocyte infusions following hematopoietic cell transplantation. In this perspective paper a mathematical basis for personalized dosing of CA…
Universal characterization of epitope immunodominance from a multi-scale model of clonal competition in germinal centers
We introduce a novel, multi-scale model for affinity maturation, which aims to capture the intra-clonal, inter-clonal and epitope-specific organization of the B cell population in a germinal center. We describe the evolu…
Implementation of an AI-based MRD evaluation and prediction model for multiple myeloma
With the application of hematopoietic stem cell transplantation and new drugs, the progression-free survival rate and overall survival rate of multiple myeloma have been greatly improved, but it is still considered as a …
PrognosisAssessment of Clonal Hematopoiesis of Indeterminate Potential from Cardiac Magnetic Resonance Imaging using Deep Learning in a Cardio-oncology Population
Background: We propose a novel method to identify who may likely have clonal hematopoiesis of indeterminate potential (CHIP), a condition characterized by the presence of somatic mutations in hematopoietic stem cells wit…
Deep LearningDiagnosticEarly life imprints the hierarchy of T cell clone sizes
The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of…
Human Aging