ArticlePLoS computational biology2009
Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib.
Article in PLoS computational biology, 2009. 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.
- Predictive nonlinear modeling of malignant myelopoiesis and tyrosine kinase inhibitor therapy.eLife · 2023Article
- Stability of Control Networks in Autonomous Homeostatic Regulation of Stem Cell Lineages.Bulletin of mathematical biology · 2018Article
- Determining the control networks regulating stem cell lineages in colonic crypts.Journal of theoretical biology · 2017Article
- Long-term treatment effects in chronic myeloid leukemia.Journal of mathematical biology · 2017Article
- Determining the role of inflammation in the selection of JAK2 mutant cells in myeloproliferative neoplasms.Journal of theoretical biology · 2017Article
- Article
- Optimized Treatment Schedules for Chronic Myeloid Leukemia.PLoS computational biology · 2016Article
- Feedback mechanisms control coexistence in a stem cell model of acute myeloid leukaemia.Journal of theoretical biology · 2016Article
- To wake up cancer stem cells, or to let them sleep, that is the question.Cancer science · 2016Review
- Robustness of differentiation cascades with symmetric stem cell division.Journal of the Royal Society, Interface · 2014Article
- The mathematician versus the malignancy.Nature medicine · 2014Article
- The ecology in the hematopoietic stem cell niche determines the clinical outcome in chronic myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Selection pressure exerted by imatinib therapy leads to disparate outcomes of imatinib discontinuation trials.Haematologica · 2012Article
- Therapy of chronic myeloid leukaemia can benefit from the activation of stem cells: simulation studies of different treatment combinations.British journal of cancer · 2012Article
- Review
- A simple mathematical model based on the cancer stem cell hypothesis suggests kinetic commonalities in solid tumor growth.PloS one · 2012Article
- Role of STAT3 in Transformation and Drug Resistance in CML.Frontiers in oncology · 2012Article
- Chronic myeloid leukemia stem cells in the era of targeted therapies: resistance, persistence and long-term dormancy.Oncotarget · 2011Article
- A multicellular basis for the origination of blast crisis in chronic myeloid leukemia.Cancer research · 2011Article
- The Ph-positive and Ph-negative myeloproliferative neoplasms: some topical pre-clinical and clinical issues.Haematologica · 2011Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic.
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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.