ArticleInternational journal of molecular sciences2023
A Receptor Tyrosine Kinase Inhibitor Sensitivity Prediction Model Identifies AXL Dependency in Leukemia.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- CREB1 and GSK3 Isoforms as Potential Adaptive Signaling Nodes in PI3K/Akt/mTOR Inhibitor Treated Philadelphia Chromosome-Positive B-ALL.International journal of molecular sciences · 2026Article
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- Artificial intelligence and anti-cancer drugs' response.Acta pharmaceutica Sinica. B · 2025Review
- A Simple Machine Learning-Based Quantitative Structure-Activity Relationship Model for Predicting pICPharmaceuticals (Basel, Switzerland) · 2025Article
- The Role of Changes in the Redox Status in the Pathogenesis of Chronic Lymphocytic Leukemia.Doklady. Biochemistry and biophysics · 2024Review
- AlphaML: A clear, legible, explainable, transparent, and elucidative binary classification platform for tabular data.Patterns (New York, N.Y.) · 2024Article
- PLK1 as a cooperating partner for BCL2-mediated antiapoptotic program in leukemia.Blood cancer journal · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite incredible progress in cancer treatment, therapy resistance remains the leading limiting factor for long-term survival. During drug treatment, several genes are transcriptionally upregulated to mediate drug tolerance. Using highly variable genes and pharmacogenomic data for acute myeloid leukemia (AML), we developed a drug sensitivity prediction model for the receptor tyrosine kinase inhibitor sorafenib and achieved more than 80% prediction accuracy. Furthermore, by using Shapley additive explanations for determining leading features, we identified AXL as an important feature for drug resistance. Drug-resistant patient samples displayed enrichment of protein kinase C (PKC) signaling, which was also identified in sorafenib-treated FLT3-ITD-dependent AML cell lines by a peptide-based kinase profiling assay. Finally, we show that pharmacological inhibition of tyrosine kinase activity enhances AXL expression, phosphorylation of the PKC-substrate cyclic AMP response element binding (CREB) protein, and displays synergy with AXL and PKC inhibitors. Collectively, our data suggest an involvement of AXL in tyrosine kinase inhibitor resistance and link PKC activation as a possible signaling mediator.
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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.