ArticleLeukemia2010
Long-term exposure of leukemia cells to multi-targeted tyrosine kinase inhibitor induces activations of AKT, ERK and STAT5 signaling via epigenetic silencing of the PTEN gene.
Article in Leukemia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Dynamic epigenetic changes to VHL occur with sunitinib in metastatic clear cell renal cancer.Oncotarget · 2016Trial
- Role of epigenetic in cancer biology, in hematologic malignancies and in anticancer therapy.Frontiers in molecular medicine · 2024Review
- Article
- Current Views on the Interplay between Tyrosine Kinases and Phosphatases in Chronic Myeloid Leukemia.Cancers · 2021Review
- Article
- Histone Acetyltransferase (HAT) P300/CBP Inhibitors Induce Synthetic Lethality in PTEN-Deficient Colorectal Cancer Cells through Destabilizing AKT.International journal of biological sciences · 2020Article
- S100A8 and S100A9 Promote Apoptosis of Chronic Eosinophilic Leukemia Cells.Frontiers in immunology · 2020Article
- Clofarabine‑phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase‑dependent apoptosis.Molecular medicine reports · 2019Article
- Inhibitors of the PI3K/mTOR pathway prevent STAT5 phosphorylation inOncotarget · 2017Article
- MiR-211/STAT5A Signaling Modulates Migration of Mesenchymal Stem Cells to Improve its Therapeutic Efficacy.Stem cells (Dayton, Ohio) · 2016Article
- The Eosinophil in Health and Disease: from Bench to Bedside and Back.Clinical reviews in allergy & immunology · 2016Review
- Targeting phosphatidylinositol-3-kinase pathway for the treatment of Philadelphia-negative myeloproliferative neoplasms.Molecular cancer · 2015Review
- Tetraspanin Family Member, CD82, Regulates Expression of EZH2 via Inactivation of p38 MAPK Signaling in Leukemia Cells.PloS one · 2015Article
- Downregulation of miR-217 correlates with resistance of Ph(+) leukemia cells to ABL tyrosine kinase inhibitors.Cancer science · 2014Article
- Article
- Application of multiplexed kinase inhibitor beads to study kinome adaptations in drug-resistant leukemia.PloS one · 2013Article
- Enhanced ABL-inhibitor-induced MAPK-activation in T315I-BCR-ABL-expressing cells: a potential mechanism of altered leukemogenicity.Journal of cancer research and clinical oncology · 2012Article
- Imatinib causes epigenetic alterations of PTEN gene via upregulation of DNA methyltransferases and polycomb group proteins.Blood cancer journal · 2011Article
- Cytochrome P450 2J2 is highly expressed in hematologic malignant diseases and promotes tumor cell growth.The Journal of pharmacology and experimental therapeutics · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imatinib induces complete molecular response in patients with chronic myeloid leukemia (CML) and chronic eosinophilic leukemia (CEL). However, development of resistance to imatinib has emerged as an important clinical problem for molecular-targeted therapy in CML and CEL. In this study, we have established the imatinib-resistant CEL EOL-1 sub-lines (designated as EOL-1R) by culturing cells with increasing concentrations of imatinib for 6 months. Interestingly, EOL-1R cells showed epigenetic silencing of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene. Exposure of EOL-1R cells to imatinib failed to dephosphorylate AKT, ERK and STAT5, although PDGFRalpha was effectively inactivated. The forced expression of PTEN negatively regulated these signal pathways and sensitized EOL-1R cells to imatinib. Notably, hypermethylation of the promoter region of the PTEN gene in association with the downregulation of this gene's transcripts was identified in imatinib-resistant leukemia cells isolated from individuals with CEL, CML and Philadelphia-positive acute lymphoblastic leukemia. In addition, anti-epigenetic agents restored PTEN expression, resulting in the sensitization of EOL-1R cells to imatinib. Taken together, epigenetic silence of PTEN is one of the mechanisms that cause drug resistance in individuals with leukemia after exposure to imatinib. Anti-epigenetic agents may be useful for overcoming drug resistance in such a case.
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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.