ArticleMolecular & cellular proteomics : MCP2012
Phosphoproteomic analysis of leukemia cells under basal and drug-treated conditions identifies markers of kinase pathway activation and mechanisms of resistance.
Article in Molecular & cellular proteomics : MCP, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
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- SFX-01 is therapeutic against myeloproliferative disorders caused by activating mutations in Shp2.EMBO molecular medicine · 2025Article
- Putative role of TMEM165 in congenital cardiomyopathies.Frontiers in molecular neuroscience · 2025Review
- The ric-8b protein (resistance to inhibitors of cholinesterase 8b) is key to preserving contractile function in the adult heart.The Journal of biological chemistry · 2024Article
- Phosphoproteomic profiling of early rheumatoid arthritis synovium reveals active signalling pathways and differentiates inflammatory pathotypes.Arthritis research & therapy · 2024Article
- Principles of phosphoproteomics and applications in cancer research.The Biochemical journal · 2023Article
- Mass Spectrometry Contribution to Pediatric Cancers Research.Medicina (Kaunas, Lithuania) · 2023Review
- Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes.Signal transduction and targeted therapy · 2023Article
- Pharmacological approaches to understanding protein kinase signaling networks.Frontiers in pharmacology · 2023Review
- The cytotoxic action of BCI is not dependent on its stated DUSP1 or DUSP6 targets in neuroblastoma cells.FEBS open bio · 2022Article
- eEF2K Activity Determines Synergy to Cotreatment of Cancer Cells With PI3K and MEK Inhibitors.Molecular & cellular proteomics : MCP · 2022Article
- MCTR3 reprograms arthritic monocytes to upregulate Arginase-1 and exert pro-resolving and tissue-protective functions in experimental arthritis.EBioMedicine · 2022Article
- Application of High Throughput Technologies in the Development of Acute Myeloid Leukemia Therapy: Challenges and Progress.International journal of molecular sciences · 2022Review
- Understanding Retinoblastoma Post-Translational Regulation for the Design of Targeted Cancer Therapies.Cancers · 2022Review
- Computational Analysis of Cholangiocarcinoma Phosphoproteomes Identifies Patient-Specific Drug Targets.Cancer research · 2021Article
- A novel dual HDAC and HSP90 inhibitor, MPT0G449, downregulates oncogenic pathways in human acute leukemia in vitro and in vivo.Oncogenesis · 2021Article
- Combining Mass Spectrometry-Based Phosphoproteomics with a Network-Based Approach to Reveal FLT3-Dependent Mechanisms of Chemoresistance.Proteomes · 2021Review
- Drug ranking using machine learning systematically predicts the efficacy of anti-cancer drugs.Nature communications · 2021Article
- Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation.Nature communications · 2020Article
- Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines.Molecular & cellular proteomics : MCP · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase signaling is fundamental to cell homeostasis and is deregulated in all cancers but varies between patients. Understanding the mechanisms underlying this heterogeneity is critical for personalized targeted therapies. Here, we used a recently established LC-MS/MS platform to profile protein phosphorylation in acute myeloid leukemia cell lines with different sensitivities to kinase inhibitors. The compounds used in this study were originally developed to target Janus kinase, phosphatidylinositol 3-kinase, and MEK. After further validation of the technique, we identified several phosphorylation sites that were inhibited by these compounds but whose intensities did not always correlate with growth inhibition sensitivity. In contrast, several hundred phosphorylation sites that correlated with sensitivity/resistance were not in general inhibited by the compounds. These results indicate that markers of pathway activity may not always be reliable indicators of sensitivity of cancer cells to inhibitors that target such pathways, because the activity of parallel kinases can contribute to resistance. By mining our data we identified protein kinase C isoforms as one of such parallel pathways being more active in resistant cells. Consistent with the view that several parallel kinase pathways were contributing to resistance, inhibitors that target protein kinase C, MEK, and Janus kinase potentiated each other in arresting the proliferation of multidrug-resistant cells. Untargeted/unbiased approaches, such as the one described here, to quantify the activity of the intended target kinase pathway in concert with the activities of parallel kinase pathways will be invaluable to personalize therapies based on kinase inhibitors.
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