The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Stat3 signaling in acute myeloid leukemia: ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor
Open accessAbstract
Acute myeloid leukemia (AML) is an aggressive malignancy with a relapse rate approaching 50%, despite aggressive chemotherapy. New therapies for AML are targeted at signal transduction pathways known to support blast survival, such as the Stat3 pathway. Aberrant activation of Stat3 has been demonstrated in many different malignancies, including AML, and this finding is frequently associated with more aggressive disease. The objectives of this study were: (1) to characterize Stat3 signaling patterns in AML cells lines and primary pediatric samples; and (2) to test the efficacy and potency of a novel Stat3 inhibitor in inducing apoptosis in AML cells. We found that Stat3 was constitutively activated in 6 of 7 AML cell lines and 6 of 18 primary pediatric AML samples. Moreover, constitutively phosphorylated Stat3 was frequent in samples with normal karyotype but uncommon in samples with t(8;21). Most cell lines and primary samples responded to G-CSF stimulation, although the sensitivity and magnitude of the response varied dramatically. Our novel small-molecule Stat3 inhibitor, C188-9, inhibited G-CSF–induced Stat3 phosphorylation, induced apoptosis in AML cell lines and primary samples, and inhibited AML blast colony formation with potencies in the low micromolar range. Therefore, Stat3 inhibition may be a valuable strategy for targeted therapies for AML.
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Cites
Function of Mitochondrial Stat3 in Cellular Respiration
Wegrzyn, J., Potla, R., Chwae, Y.-J., Sepuri, N. B. V., Zhang, Q., Koeck, T., Derecka, M., Szczepanek, K., Szelag, M., Gornicka, A., et al. (2009) · Science · doi:10.1126/science.1164551 · Cited by 1,014
Enhanced DNA-Binding Activity of a Stat3-Related Protein in Cells Transformed by the Src Oncoprotein
Yu, C.-L., Meyer, D. J., Campbell, G. S., Larner, A. C., Carter-Su, C., Schwartz, J., & Jove, R. (1995) · Science · doi:10.1126/science.7541555 · Cited by 931
Song, H., Wang, R., Wang, S., & Lin, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409894102 · Cited by 504
Welte, T., Zhang, S. S. M., Wang, T., Zhang, Z., Hesslein, D. G. T., Yin, Z., Kano, A., Iwamoto, Y., Li, E., Craft, J. E., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0237137100 · Cited by 381
Turkson, J., Zhang, S., Palmer, J., Kay, H., Stanko, J., Mora, L. B., Sebti, S., Yu, H., & Jove, R. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.1533.3.12 · Cited by 188
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
Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery
Hu, Y., Dong, Z., & Liu, K. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-02949-5 · Cited by 268
Dong, J., Cheng, X.-D., Zhang, W.-D., & Qin, J.-J. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00629 · Cited by 232
Silva, K. A. S., Dong, J., Dong, Y., Dong, Y., Schor, N., Tweardy, D. J., Zhang, L., & Mitch, W. E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.641514 · Cited by 229
Self-citationPedroza, M., Le, T. T., Lewis, K., Karmouty‐Quintana, H., To, S., George, A. T., Blackburn, M. R., Tweardy, D. J., & Agarwal, S. K. (2016) · The FASEB Journal · doi:10.1096/fj.15-273953 · Cited by 193
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Metadata
- Authors
- Redell, M. S., Ruiz, M. J., Alonzo, T. A., Gerbing, R. B., & Tweardy, D. J.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-05-26
- Volume
- 117
- Issue
- 21
- Pages
- 5701-5709
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2091660633
- Cited by
- 257
- References
- 5
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Redell, M. S., Ruiz, M. J., Alonzo, T. A., Gerbing, R. B., & Tweardy, D. J. (2011). Stat3 signaling in acute myeloid leukemia: ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor. Blood. https://doi.org/10.1182/blood-2010-04-280123
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