ArticleProceedings of the National Academy of Sciences of the United States of America2014
The ecology in the hematopoietic stem cell niche determines the clinical outcome in chronic myeloid leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 67 citations in OpenAlex.
- Simulation-based inference of cell migration dynamics in complex spatial environments.NPJ systems biology and applications · 2026Article
- Modeling, analysis and numerical simulation of chronic myeloid leukemia.Theory in biosciences = Theorie in den Biowissenschaften · 2026Article
- Dynamically adjusted cell fate decisions and resilience to mutant invasion during steady-state hematopoiesis revealed by an experimentally parameterized mathematical model.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The importance of host physical niches for the stability of gut microbiome composition.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Computational modeling reveals key factors driving treatment-free remission in chronic myeloid leukemia patients.NPJ systems biology and applications · 2024Article
- FitMultiCell: simulating and parameterizing computational models of multi-scale and multi-cellular processes.Bioinformatics (Oxford, England) · 2023Article
- Predictive nonlinear modeling of malignant myelopoiesis and tyrosine kinase inhibitor therapy.eLife · 2023Article
- Computational modeling of stem and progenitor cell kinetics identifies plausible hematopoietic lineage hierarchies.iScience · 2021Article
- Importance of Stability Analysis When Using Nonlinear Semimechanistic Models to Describe Drug-Induced Hematotoxicity.CPT: pharmacometrics & systems pharmacology · 2020Article
- Mapping and targeting of the leukemic microenvironment.The Journal of experimental medicine · 2020Review
- Feedback regulation in a stem cell model with acute myeloid leukaemia.BMC systems biology · 2018Article
- Chemokines as a Conductor of Bone Marrow Microenvironment in Chronic Myeloid Leukemia.International journal of molecular sciences · 2017Review
- CBP/Catenin antagonists: Targeting LSCs' Achilles heel.Experimental hematology · 2017Review
- Identifying niche-mediated regulatory factors of stem cell phenotypic state: a systems biology approach.FEBS letters · 2017Review
- The proportion of cancer-related entries in PubMed has increased considerably; is cancer truly "The Emperor of All Maladies"?PloS one · 2017Article
- Article
- Systems Analysis of the Dynamic Inflammatory Response to Tissue Damage Reveals Spatiotemporal Properties of the Wound Attractant Gradient.Current biology : CB · 2016Article
- Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: An Evolving Paradigm of Molecularly Targeted Therapy.Molecular diagnosis & therapy · 2016Review
- Feedback mechanisms control coexistence in a stem cell model of acute myeloid leukaemia.Journal of theoretical biology · 2016Article
- Chronic myeloid leukemia: advances in understanding disease biology and mechanisms of resistance to tyrosine kinase inhibitors.Current hematologic malignancy reports · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Chronic myeloid leukemia (CML) is a blood disease that disrupts normal function of the hematopoietic system. Despite the great progress made in terms of molecular therapies for CML, there remain large gaps in our understanding. By comparing mathematical models that describe CML progression and etiology we sought to identify those models that provide the best description of disease dynamics and their underlying mechanisms. Data for two clinical outcomes--disease remission or relapse--are considered, and we investigate these using Bayesian inference techniques throughout. We find that it is not possible to choose between the models based on fits to the data alone; however, by studying model predictions we can discard models that fail to take niche effects into account. More detailed analysis of the remaining models reveals mechanistic differences: for one model, leukemia stem cell dynamics determine the disease outcome; and for the other model disease progression is determined at the stage of progenitor cells, in particular by differences in progenitor death rates. This analysis also reveals distinct transient dynamics that will be experimentally accessible, but are currently at the limits of what is possible to measure. To resolve these differences we need to be able to probe the hematopoietic stem cell niche directly. Our analysis highlights the importance of further mapping of the bone marrow hematopoietic niche microenvironment as the "ecological" interactions between cells in this niche appear to be intricately linked to disease outcome.
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Registered trials
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.