ArticleBritish journal of cancer2012
Therapy of chronic myeloid leukaemia can benefit from the activation of stem cells: simulation studies of different treatment combinations.
Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- Modelling post-chemotherapy stem cell dynamics in the bone marrow niche of AML patients.Scientific reports · 2024Article
- HSC Niche Dynamics in Regeneration, Pre-malignancy, and Cancer: Insights From Mathematical Modeling.Stem cells (Dayton, Ohio) · 2023Article
- Recreating the Bone Marrow Microenvironment to Model Leukemic Stem Cell Quiescence.Frontiers in cell and developmental biology · 2021Article
- Differential response to cytotoxic therapy explains treatment dynamics of acute myeloid leukaemia patients: insights from a mathematical modelling approach.Journal of the Royal Society, Interface · 2020Article
- Quantitative prediction of long-term molecular response in TKI-treated CML - Lessons from an imatinib versus dasatinib comparison.Scientific reports · 2018Article
- Long-term treatment effects in chronic myeloid leukemia.Journal of mathematical biology · 2017Article
- CDKIs p18(INK4c) and p57(Kip2) are involved in quiescence of CML leukemic stem cells after treatment with TKI.Cell cycle (Georgetown, Tex.) · 2016Article
- Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia.Scientific reports · 2016Article
- A Review of Mathematical Models for Leukemia and Lymphoma.Drug discovery today. Disease models · 2015Article
- A global assessment of stem cell engineering.Tissue engineering. Part A · 2014Article
- Merging concepts - coupling an agent-based model of hematopoietic stem cells with an ODE model of granulopoiesis.BMC systems biology · 2013Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNewly diagnosed patients with chronic myeloid leukaemia (CML) are currently treated with tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib or dasatinib. However, incomplete eradication of residual disease is a general problem of long-term TKI therapy. Activation of mouse haematopoietic stem cells by interferon-α (IFNα) stimulated the discussion of whether a combination treatment leads to accelerated eradication of the CML clone.
methodsWe base our simulation approach on a mathematical model describing human CML as a competition phenomenon between normal and malignant cells. We amend this model to incorporate the description of IFNα activity and simulate different scenarios for potential treatment combinations.
resultsWe demonstrate that the overall sensitivity of CML stem cells to IFNα activation is a crucial determinant for the benefit of a potential combination therapy. We furthermore show that pulsed IFNα together with continuous TKI administration is the most promising strategy for a combination treatment in which the therapeutic benefit prevails adverse side effects.
conclusionOur modelling approach is a highly beneficial tool to quantitatively address the competition between normal and leukaemic haematopoiesis in treated CML patients. We derive testable predictions for different experimental settings that are suggested before the clinical implementation of the combination treatment.
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