ArticleLeukemia2017
Identification and characterization of activating ABL1 1b kinase mutations: impact on sensitivity to ATP-competitive and allosteric ABL1 inhibitors.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Comprehensive resistance profiling of chronic myeloid leukaemia associated ABL1 variants against five tyrosine kinase inhibitors using prime editing.Nature biomedical engineering · 2026Article
- Ponatinib: A Review of the History of Medicinal Chemistry behind Its Development.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain.bioRxiv : the preprint server for biology · 2024Article
- Activity-based CRISPR scanning uncovers allostery in DNA methylation maintenance machinery.eLife · 2023Article
- Review
- Investigation on the interaction behavior of afatinib, dasatinib, and imatinib docked to the BCR-ABL protein.Journal of molecular modeling · 2021Article
- ABL1 Is a Prognostic Marker and Associated with Immune Infiltration in Hepatocellular Carcinoma.Journal of oncology · 2021Article
- Conformational states dynamically populated by a kinase determine its function.Science (New York, N.Y.) · 2020Article
- In silico analysis of alternative splicing on drug-target gene interactions.Scientific reports · 2020Article
- Defining the landscape of ATP-competitive inhibitor resistance residues in protein kinases.Nature structural & molecular biology · 2020Article
- Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure.The New England journal of medicine · 2019Article
- Understanding molecular mechanisms in cell signaling through natural and artificial sequence variation.Nature structural & molecular biology · 2019Review
- The Src module: an ancient scaffold in the evolution of cytoplasmic tyrosine kinases.Critical reviews in biochemistry and molecular biology · 2018Review
- EnABLing Tumor Growth and Progression: Recent progress in unraveling the functions of ABL kinases in solid tumor cells.Current pharmacology reports · 2018Article
- Atomic view of the energy landscape in the allosteric regulation of Abl kinase.Nature structural & molecular biology · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although pathologically activated ABL1 fusion kinases represent well-validated therapeutic targets, tumor genomic sequencing has identified numerous point mutations in the ABL1 proto-oncogene of unclear significance. Here we describe ten novel ABL1 1b point mutations, including two from clinical isolates, that cause constitutive kinase activation and cellular transformation. All mutants retained sensitivity to ATP-competitive tyrosine kinase inhibitors (TKIs). Several substitutions cluster near the myristoyl-binding pocket, the target of ABL001, a novel clinically active allosteric kinase inhibitor that mimics the autoinhibitory myristoyl group, and likely activate the kinase by relieving physiologic autoinhibition. In addition, several mutations activate the kinase and confer resistance to allosteric inhibition despite a lack of proximity to this region. We demonstrate that BCR-ABL1 and ABL1 1b point mutations can co-exist in a proportion of clinical cases as a consequence of the chromosome 9 breakpoint location. Collectively, our findings support clinical investigation of ATP-competitive TKIs in malignancies harboring ABL1 point mutations, and sequencing of BCR-ABL1 and ABL1 1b in patients with acquired resistance to allosteric ABL1 inhibitors.
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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 Socratic graph.