ArticleLeukemia2015
Sustained inhibition of STAT5, but not JAK2, is essential for TKI-induced cell death in chronic myeloid leukemia.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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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
20 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Review
- Gene Transcription as a Therapeutic Target in Leukemia.International journal of molecular sciences · 2021Review
- Targeted drug delivery strategies for precision medicines.Nature reviews. Materials · 2021Article
- Combined effects on leukemia cell growth by targeting sphingosine kinase 1 and sirtuin 1 signaling.Experimental and therapeutic medicine · 2020Article
- Nanoparticles Targeting STATs in Cancer Therapy.Cells · 2019Review
- 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
- Low UBE4B expression increases sensitivity of chemoresistant neuroblastoma cells to EGFR and STAT5 inhibition.Cancer biology & therapy · 2019Article
- Suppressor of cytokine signalling-2 limits IGF1R-mediated regulation of epithelial-mesenchymal transition in lung adenocarcinoma.Cell death & disease · 2018Article
- The T-cell leukemia-associated ribosomal RPL10 R98S mutation enhances JAK-STAT signaling.Leukemia · 2018Article
- Minimal Residual Disease Eradication in CML: Does It Really Matter?Current hematologic malignancy reports · 2017Review
- CM363, a novel naphthoquinone derivative which acts as multikinase modulator and overcomes imatinib resistance in chronic myelogenous leukemia.Oncotarget · 2017Article
- Article
- Prolonged cellular midostaurin retention suggests potential alternative dosing strategies for FLT3-ITD-positive leukemias.Leukemia · 2016Article
- Ursolic acid-mediated apoptosis of K562 cells involves Stat5/Akt pathway inhibition through the induction of Gfi-1.Scientific reports · 2016Article
- High IL-7 levels in the bone marrow microenvironment mediate imatinib resistance and predict disease progression in chronic myeloid leukemia.International journal of hematology · 2016Article
- miR141 expression is downregulated and negatively correlated with STAT5 expression in esophageal squamous cell carcinoma.Experimental and therapeutic medicine · 2016Article
- IRS2 silencing increases apoptosis and potentiates the effects of ruxolitinib in JAK2V617F-positive myeloproliferative neoplasms.Oncotarget · 2016Article
- Combined STAT3 and BCR-ABL1 inhibition induces synthetic lethality in therapy-resistant chronic myeloid leukemia.Leukemia · 2015Article
- Chaetocin antileukemia activity against chronic myelogenous leukemia cells is potentiated by bone marrow stromal factors and overcomes innate imatinib resistance.Oncogenesis · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kinase inhibitors block proliferative signals in BCR-ABL1+ leukemic cells, but their capacity to induce apoptosis is poorly understood. Initial studies suggested that very brief exposure to kinase inhibitors was sufficient to induce apoptosis in chronic myeloid leukemia (CML) cells. However, flaws in this experimental model have subsequently been identified, leading to the conclusion that apoptosis only occurs with sustained low-level kinase inhibition. Thus, the minimum duration of complete kinase inhibition required to commit CML cells to death is unknown. Here we confirm that <1 h is insufficient to induce significant commitment to death in BCR-ABL1+ cell lines and in primary CD34+ progenitor cells, and establish that commitment to cell death only occurs if kinase inhibition is maintained for 4 h or more. Remarkably, signal transducer and activator of transcription 5 (STAT5) inhibition in combination with transient (<1 h) tyrosine kinase inhibitor (TKI) exposure proved lethal for CML progenitors, despite the reactivation of Bcr-Abl after 1 h. JAK kinase inhibition did not induce cell death in combination with transient TKI exposure. Thus, STAT5 appears to be a critical determinant of the time-dependent sensitivity of CML progenitor cells to TKI treatment in a Bcr-Abl-dependent, but JAK-independent, manner. We conclude that combining kinase inhibition with STAT5 inhibition represents a promising therapeutic approach in BCR-ABL1+ leukemias.
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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.