ArticleCancer discovery2014
MEK-dependent negative feedback underlies BCR-ABL-mediated oncogene addiction.
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib.Haematologica · 2017Trial
- Cracking the resistance code: The molecular reclassification of cancer and precision therapy strategies.Seminars in cancer biology · 2025Review
- CoDIAC: A comprehensive approach for interaction analysis provides insights into SH2 domain function and regulation.Science signaling · 2025Article
- CoDIAC: A comprehensive approach for interaction analysis reveals novel insights into SH2 domain function and regulation.bioRxiv : the preprint server for biology · 2025Article
- Comprehensive evaluation of phosphoproteomic-based kinase activity inference.Nature communications · 2025Article
- Association of changes in expression ofEpigenetics · 2024Article
- The FABD domain is critical for the oncogenicity of BCR/ABL in chronic myeloid leukaemia.Cell communication and signaling : CCS · 2024Article
- Comprehensive molecular characterization of a rare case of Philadelphia chromosome-positive acute myeloid leukemia.Cold Spring Harbor molecular case studies · 2022Article
- KSTAR: An algorithm to predict patient-specific kinase activities from phosphoproteomic data.Nature communications · 2022Article
- Pterostilbene downregulates BCR/ABL and induces apoptosis of T315I-mutated BCR/ABL-positive leukemic cells.Scientific reports · 2022Article
- An overview of agents and treatments for PDGFRA-mutated gastrointestinal stromal tumors.Frontiers in oncology · 2022Review
- Effect of HSP90AB1 and CC domain interaction on Bcr-Abl protein cytoplasm localization and function in chronic myeloid leukemia cells.Cell communication and signaling : CCS · 2021Article
- The N-terminal domain of the non-receptor tyrosine kinase ABL confers protein instability and suppresses tumorigenesis.The Journal of biological chemistry · 2020Article
- Efficient disruption of bcr-abl gene by CRISPR RNA-guided FokI nucleases depresses the oncogenesis of chronic myeloid leukemia cells.Journal of experimental & clinical cancer research : CR · 2019Article
- Developmental and cancer-associated plasticity of DNA replication preferentially targets GC-poor, lowly expressed and late-replicating regions.Nucleic acids research · 2018Article
- Mechanisms of Resistance to ABL Kinase Inhibition in Chronic Myeloid Leukemia and the Development of Next Generation ABL Kinase Inhibitors.Hematology/oncology clinics of North America · 2017Review
- The targetable role of herpes virus-associated ubiquitin-specific protease (HAUSP) in p190 BCR-ABL leukemia.Oncology letters · 2016Article
- An Activating KIT Mutation Induces Crizotinib Resistance in ROS1-Positive Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2016Article
- The Philadelphia chromosome in leukemogenesis.Chinese journal of cancer · 2016Review
- Chronic myeloid leukemia: advances in understanding disease biology and mechanisms of resistance to tyrosine kinase inhibitors.Current hematologic malignancy reports · 2015Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledThe clinical experience with BCR-ABL tyrosine kinase inhibitors (TKI) for the treatment of chronic myelogenous leukemia (CML) provides compelling evidence for oncogene addiction. Yet, the molecular basis of oncogene addiction remains elusive. Through unbiased quantitative phosphoproteomic analyses of CML cells transiently exposed to BCR-ABL TKI, we identified persistent downregulation of growth factor receptor (GF-R) signaling pathways. We then established and validated a tissue-relevant isogenic model of BCR-ABL-mediated addiction, and found evidence for myeloid GF-R signaling pathway rewiring that profoundly and persistently dampens physiologic pathway activation. We demonstrate that eventual restoration of ligand-mediated GF-R pathway activation is insufficient to fully rescue cells from a competing apoptotic fate. In contrast to previous work with BRAF(V600E) in melanoma cells, feedback inhibition following BCR-ABL TKI treatment is markedly prolonged, extending beyond the time required to initiate apoptosis. Mechanistically, BCR-ABL-mediated oncogene addiction is facilitated by persistent high levels of MAP-ERK kinase (MEK)-dependent negative feedback. SIGNIFICANCE: We found that BCR–ABL can confer addiction in vitro by rewiring myeloid GF-R signaling through establishment of MEK-dependent negative feedback. Our findings predict that deeper, more durable responses to targeted agents across a range of malignancies may be facilitated by maintaining negative feedback concurrently with oncoprotein inhibition.
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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 OpenQuestion graph.