ArticleProceedings of the National Academy of Sciences of the United States of America2014
Molecular dynamics reveal BCR-ABL1 polymutants as a unique mechanism of resistance to PAN-BCR-ABL1 kinase inhibitor therapy.
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 36 papers.
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Who cites it
36 citing papers in PubMed, 80 citations in OpenAlex.
- Trial
- Mutation analysis of BCR-ABL1 kinase domain in chronic myeloid leukemia patients with tyrosine kinase inhibitors resistance: a Malaysian cohort study.BMC research notes · 2024Article
- Resistance mutations in CML and how we approach them.Hematology. American Society of Hematology. Education Program · 2023Review
- European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia.Leukemia · 2023Review
- Development of a First-in-Class Small-Molecule Inhibitor of the C-Terminal Hsp90 Dimerization.ACS central science · 2022Article
- Overcoming Resistance to Kinase Inhibitors: The Paradigm of Chronic Myeloid Leukemia.OncoTargets and therapy · 2022Review
- Molecular rationale for SARS-CoV-2 spike circulating mutations able to escape bamlanivimab and etesevimab monoclonal antibodies.Scientific reports · 2021Article
- Article
- Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.Signal transduction and targeted therapy · 2021Review
- Multitarget Biological Profiling of New Naphthoquinone and Anthraquinone-Based Derivatives for the Treatment of Alzheimer's Disease.ACS chemical neuroscience · 2021Article
- Asciminib and ponatinib exert synergistic anti-neoplastic effects on CML cells expressingAmerican journal of cancer research · 2021Article
- Computational Alanine Scanning and Structural Analysis of the SARS-CoV-2 Spike Protein/Angiotensin-Converting Enzyme 2 Complex.ACS nano · 2020Article
- Cumulative mechanism of several major imatinib-resistant mutations in Abl kinase.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Mutations in the BCR-ABL1 kinase domain in patients with chronic myeloid leukaemia treated with TKIs or at diagnosis.Oncology letters · 2020Article
- Emerging roles of the αC-β4 loop in protein kinase structure, function, evolution, and disease.IUBMB life · 2020Review
- CDK4/CDK6 inhibition as a novel strategy to suppress the growth and survival of BCR-ABL1EBioMedicine · 2019Article
- Dichloro-Phenyl-Benzotriazoles: A New Selective Class of Human Respiratory Syncytial Virus Entry Inhibitors.Frontiers in chemistry · 2019Article
- Chronic myeloid leukemia: the paradigm of targeting oncogenic tyrosine kinase signaling and counteracting resistance for successful cancer therapy.Molecular cancer · 2018Review
- β-Catenin in desmoid-type fibromatosis: deep insights into the role of T41A and S45F mutations on protein structure and gene expression.Molecular oncology · 2017Article
- Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The acquisition of mutations within the BCR-ABL1 kinase domain is frequently associated with tyrosine kinase inhibitor (TKI) failure in chronic myeloid leukemia. Sensitive sequencing techniques have revealed a high prevalence of compound BCR-ABL1 mutations (polymutants) in patients failing TKI therapy. To investigate the molecular consequences of such complex mutant proteins with regards to TKI resistance, we determined by cloning techniques the presence of polymutants in a cohort of chronic-phase patients receiving imatinib followed by dasatinib therapy. The analysis revealed a high frequency of polymutant BCR-ABL1 alleles even after failure of frontline imatinib, and also the progressive exhaustion of the pool of unmutated BCR-ABL1 alleles over the course of sequential TKI therapy. Molecular dynamics analyses of the most frequent polymutants in complex with TKIs revealed the basis of TKI resistance. Modeling of BCR-ABL1 in complex with the potent pan-BCR-ABL1 TKI ponatinib highlighted potentially effective therapeutic strategies for patients carrying these recalcitrant and complex BCR-ABL1 mutant proteins while unveiling unique mechanisms of escape to ponatinib therapy.
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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.