ArticleLeukemia2003
In BCR-ABL-positive cells, STAT-5 tyrosine-phosphorylation integrates signals induced by imatinib mesylate and Ara-C.
Article in Leukemia, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 36 citations in OpenAlex.
- Induction of GD3/α1-adrenergic receptor/transglutaminase 2-mediated erythroid differentiation in chronic myelogenous leukemic K562 cells.Oncotarget · 2017Article
- Design, Synthesis, and Antitumor Evaluation of 4-Amino-(1ACS medicinal chemistry letters · 2016Article
- Signal Transducers and Activators of Transcription (STAT) Regulatory Networks in Marine Organisms: From Physiological Observations towards Marine Drug Discovery.Marine drugs · 2015Review
- Epo-induced erythroid maturation is dependent on Plcγ1 signaling.Cell death and differentiation · 2015Article
- Murine B-1 B cell progenitors initiate B-acute lymphoblastic leukemia with features of high-risk disease.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Review
- Targeting MCL-1 sensitizes FLT3-ITD-positive leukemias to cytotoxic therapies.Blood cancer journal · 2012Article
- Intracellular retention of ABL kinase inhibitors determines commitment to apoptosis in CML cells.PloS one · 2012Article
- Novel pathway in Bcr-Abl signal transduction involves Akt-independent, PLC-gamma1-driven activation of mTOR/p70S6-kinase pathway.Oncogene · 2010Article
- GATA-1 and Gfi-1B interplay to regulate Bcl-xL transcription.Molecular and cellular biology · 2007Article
- JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis.Leukemia · 2004Review
- Organic Nanoparticles as Drug Delivery Systems and Their Potential Role in the Treatment of Chronic Myeloid Leukemia.Technology in cancer research & treatmentReview
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In BCR-ABL-positive cells, the transcription factor STAT-5 is constitutively activated by tyrosine phosphorylation. STAT-5 activation results in upregulation of bcl-X(L) and increased resistance to induction of apoptosis. Here, we investigated the effects of imatinib mesylate and cytosine arabinoside (Ara-C) on STAT-5 tyrosine-phosphorylation, cellular proliferation and induction of apoptosis in cell lines and primary hematopoietic cells. Imatinib mesylate treatment strongly suppressed STAT-5 tyrosine-phosphorylation in K562 and primary CML blasts. In contrast to JAK-2 and PI-3-kinase inhibition, exposure of K562 cells to imatinib mesylate resulted in obvious suppression of proliferation. Reduced cell growth was due to specific induction of caspase activation followed by apoptotic cell death. In addition, we investigated the effects of Ara-C on STAT-5 tyrosine-phosphorylation. Exposure to Ara-C resulted in significant downregulation of STAT-5 tyrosine-phosphorylation and inhibition of DNA binding. Treatment of K562 cells with Ara-C in combination with imatinib mesylate revealed synergistic effects at the level of STAT-5 tyrosine-phosphorylation and DNA binding, Hck tyrosine-phosphorylation, cell growth and induction of apoptosis. Overall, in this report we demonstrate that STAT-5 tyrosine-phosphorylation is a specific target of imatinib mesylate and Ara-C. Our results suggest that, in combination therapy, inhibition of STAT-5 tyrosine-phosphorylation may be responsible for synergistic or additive effects on BCR-ABL-positive cells.
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