Expression of granulocyte colony-stimulating factor- and granulocyte-macrophage colony-stimulating factor-associated signal transduction proteins of the JAK/STAT pathway in normal granulopoiesis and in blast cells of acute myelogenous leukemia
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Acute myelogenous leukemia (AML) is characterized by the malignant transformation of hematopoietic stem cells leading to dysregulated growth and differentiation of myeloid cells. Normally, proliferation and differentiation of myeloid cells are regulated by cytokines such as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Abnormal signaling of the signal transduction pathway from the cytokine receptors via Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) might be involved in the pathogenesis of AML. We examined whether an abnormal expression of one of the four JAKs, STAT1, STAT3, STAT5, or the tyrosine phosphatase SHP-1, a negative regulator of this pathway, is associated with malignant transformation in AML. Analysis of the expression of proteins of the JAK/STAT pathway in normal myeloid cells at three stages of maturation revealed a strong expression of all proteins in CD34+ cells, whereas the level of the proteins was significantly lower in granulocytic precursors and mature neutrophils. Furthermore, during maturation the relation of the isoforms of STAT1 and STAT3 changed from predominantly alpha to predominantly beta. Leukemic blast cells from 25 patients and 12 cell lines showed a high level of STAT proteins and SHP-1, whereas a deficiency of at least one of the four JAKs was found in 10 of 25 patients. In primary AML blast cells a deficiency of three JAKs was more common in pa…
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Striking changes in the levels of STAT3α and STAT3β have been noted during myeloid differentiation.
“Given the striking changes in the levels of STAT3α and STAT3β noted during myeloid differentiation [12–14]”
From Selective STAT3-α or -β expression reveals spliceform-specific phosphorylation kinetics, nuclear retention and distinct gene expression outcomes (2012) · cites this paper as [12]
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Caldenhoven, E., van Dijk, T. B., Solari, R., Armstrong, J., Raaijmakers, J. A. M., Lammers, J.-W. J., Koenderman, L., & de Groot, R. P. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.22.13221 · Cited by 373 · see citing works
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Singh, V. K., & Seed, T. M. (2021) · International Journal of Radiation Biology · doi:10.1080/09553002.2021.1969054 · Cited by 88 · see citing works
Ng, I. H. W., Ng, D. C. H., Jans, D. A., & Bogoyevitch, M. A. (2012) · Biochemical Journal · doi:10.1042/bj20120941 · Cited by 63 · see citing works
“…α imply that STAT3 α plays a more significant functional role in vivo , there are clear exceptions, such as the levels of STAT3 β exceeding STAT3 α during myeloid differentiation, pointing to a requirement for high STAT3 β levels to act as a mediator during these differentiation events [12–14].”
Background
- Authors
- Biethahn, S., Alves, F., Wilde, S., Hiddemann, W., & Spiekermann, K.
- Affiliations
- University of Göttingen (DE)
- Corresponding author
- Spiekermann, Karsten
- Venue
- Experimental Hematology
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 27
- Issue
- 5
- Pages
- 885-894
- ISSN
- 0301-472X (ISSN-L)
- OpenAlex
- W2018995007
- Cited by
- 74
- References
- 1
- Citations by year
- 2026: 2 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 5 · 2012: 6
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Experimental Hematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- acute myeloid leukemia, JAK/STAT signaling, granulocyte colony-stimulating factor, GM-CSF, STAT1, STAT3, STAT5, SHP-1, JAK2, TYK2, myeloid differentiation, CD34+ hematopoietic stem cells, karyotype abnormalities, clonogenicity, cytokine receptor signaling, malignant transformation, protein tyrosine phosphatase, leukemia cell proliferation
- MeSH terms
- DNA-Binding Proteins, Granulocytes, Hematopoiesis, Humans, Signal Transduction, Leukemia, Myeloid, Acute, Granulocyte-Macrophage Colony-Stimulating Factor, Granulocyte Colony-Stimulating Factor, Protein Tyrosine Phosphatases, Antigens, CD34, Cell Lineage, Intracellular Signaling Peptides and Proteins, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatase, Non-Receptor Type 11
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