The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Constitutive Stat3, Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6
Abstract
To explore the activation patterns of signal transducer and activator of transcription 3 (Stat3) in acute myeloid leukemia (AML), we examined whether the phosphorylation of tyrosine705 (Tyr705) and serine727 (Ser727) residues was abnormally regulated in cells from patients with AML. In 5 of 20 (25%) patients with AML, Stat3 was constitutively phosphorylated on Tyr705 and Ser727, which were not further up-regulated by treatment with IL-6. Furthermore, Stat3 was constitutively bound to the IRE response element in these cells as determined by electrophoretic mobility shift assay, and stimulation with IL-6 did not result in increased DNA binding. Interestingly, AML cells with constitutive Stat3 activation also secreted high levels of IL-6 protein. Treating these AML cells with anti-IL-6 resulted in restored IL-6–inducible Stat3 phosphorylation on both Tyr705 and Ser727 with low or undetectable basal phosphorylation levels in unstimulated cells. In contrast, treatment with anti-IL-1 did not result in altered Stat3 phosphorylation patterns. The constitutive IL-6 expression was associated with elevated levels of suppressor of cytokine signaling-1 (SOCS-1) and SOCS-3 mRNA expression, which were not down-regulated by anti-IL-6. These data indicate that the constitutive Stat3 activation in the investigated AML blasts is caused by high IL-6 secretion levels, thus stimulating the Jak/Stat pathway in an autocrine manner, a paracrine manner, or both.
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Impaired immune and acute-phase responses in interleukin-6-deficient mice
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Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130
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Enhanced DNA-Binding Activity of a Stat3-Related Protein in Cells Transformed by the Src Oncoprotein
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Activation and Association of Stat3 with Src in v-Src-Transformed Cell Lines
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Cited by
‘Acute myeloid leukemia: a comprehensive review and 2016 update’
De Kouchkovsky, I., & Abdul-Hay, M. (2016) · Blood Cancer Journal · doi:10.1038/bcj.2016.50 · Cited by 1,317
Nuclear factor-κB is constitutively activated in primitive human acute myelogenous leukemia cells
Guzman, M. L., Neering, S. J., Upchurch, D., Grimes, B., Howard, D. S., Rizzieri, D. A., Luger, S. M., & Jordan, C. T. (2001) · Blood · doi:10.1182/blood.v98.8.2301 · Cited by 758
Corvinus, F. M., Orth, C., Moriggl, R., Tsareva, S. A., Wagner, S., Pfitzner, E. B., Baus, D., Kaufman, R., Huber, L. A., Zatloukal, K., et al. (2005) · Neoplasia · doi:10.1593/neo.04571 · Cited by 427
Rahaman, S. O., Harbor, P. C., Chernova, O., Barnett, G. H., Vogelbaum, M. A., & Haque, S. J. (2002) · Oncogene · doi:10.1038/sj.onc.1206047 · Cited by 377
CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML)
Kelly, L. M., Yu, J.-C., Boulton, C. L., Apatira, M., Li, J., Sullivan, C. M., Williams, I., Amaral, S. M., Curley, D. P., Duclos, N., et al. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00070-3 · Cited by 305
Metadata
- Authors
- Schuringa, J.-J., Wierenga, A. T. J., Kruijer, W., & Vellenga, E.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2000-06-15
- Volume
- 95
- Issue
- 12
- Pages
- 3765-3770
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W108809021
- Cited by
- 200
- References
- 6
- FWCI
- 4.73
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Constitutive Stat3, Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. https://app.cochat.ai/papers/10.1182/blood.v95.12.3765
- The paper
- Schuringa, J.-J., Wierenga, A. T. J., Kruijer, W., & Vellenga, E. (2000). Constitutive Stat3, Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. Blood. https://doi.org/10.1182/blood.v95.12.3765
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