ArticleBMC bioinformatics2018
Computer simulations of the signalling network in FLT3
Article in BMC bioinformatics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 17 citations in OpenAlex.
- Dexamethasone Induces Changes in Osteogenic Differentiation of Human Mesenchymal Stromal Cells viaInternational journal of molecular sciences · 2021Article
- Combating drug resistance in acute myeloid leukaemia by drug rotations: the effects of quizartinib and pexidartinib.Cancer cell international · 2021Article
- Article
- Reverse engineering directed gene regulatory networks from transcriptomics and proteomics data of biomining bacterial communities with approximate Bayesian computation and steady-state signalling simulations.BMC bioinformatics · 2020Article
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMutations in the FMS-like tyrosine kinase 3 (FLT3) are associated with uncontrolled cellular functions that contribute to the development of acute myeloid leukaemia (AML). We performed computer simulations of the FLT3-dependent signalling network in order to study the pathways that are involved in AML development and resistance to targeted therapies.
resultsAnalysis of the simulations revealed the presence of alternative pathways through phosphoinositide 3 kinase (PI3K) and SH2-containing sequence proteins (SHC), that could overcome inhibition of FLT3. Inhibition of cyclin dependent kinase 6 (CDK6), a related molecular target, was also tested in the simulation but was not found to yield sufficient benefits alone.
conclusionsThe PI3K pathway provided a basis for resistance to treatments. Alternative signalling pathways could not, however, restore cancer growth signals (proliferation and loss of apoptosis) to the same levels as prior to treatment, which may explain why FLT3 resistance mutations are the most common resistance mechanism. Finally, sensitivity analysis suggested the existence of optimal doses of FLT3 and CDK6 inhibitors in terms of efficacy and toxicity.
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