ArticleThe American journal of pathology2009
Expression of activated STAT5 in neoplastic mast cells in systemic mastocytosis: subcellular distribution and role of the transforming oncoprotein KIT D816V.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 74 citations in OpenAlex.
- Design and Synthesis of BLU-654, a Potent and Selective Mutant KIT V654A Inhibitor for the Treatment of Imatinib-Resistant GIST.Journal of medicinal chemistry · 2026Article
- Mastocytosis.Nature reviews. Disease primers · 2025Review
- Fedratinib and gandotinib induce apoptosis and enhance the efficacy of tyrosine kinase inhibitors in human mast cells.American journal of cancer research · 2025Article
- Epigenetic downregulation of Socs2 contributes to mutant N-Ras-mediated hematopoietic dysregulation.Disease models & mechanisms · 2022Article
- Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis.International journal of molecular sciences · 2021Review
- Systemic Mastocytosis: Molecular Landscape and Implications for Treatment.Mediterranean journal of hematology and infectious diseases · 2021Review
- MiR-920 and LSP1 co-regulate the growth and migration of glioblastoma cells by modulation of JAK2/STAT5 pathway.Journal of bioenergetics and biomembranes · 2020Article
- Review
- Recent Advances in the Molecular Biology of Systemic Mastocytosis: Implications for Diagnosis, Prognosis, and Therapy.International journal of molecular sciences · 2020Review
- STAT5 is Expressed in CD34Cancers · 2020Article
- Oncogenic D816V-KIT signaling in mast cells causes persistent IL-6 production.Haematologica · 2020Article
- Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich's visions to precision medicine concepts.Theranostics · 2020Review
- Review
- Preclinical human models and emerging therapeutics for advanced systemic mastocytosis.Haematologica · 2018Review
- Mastocytosis: from a Molecular Point of View.Clinical reviews in allergy & immunology · 2018Review
- SRC-like adaptor protein 2 (SLAP2) is a negative regulator of KIT-D816V-mediated oncogenic transformation.Scientific reports · 2018Article
- Drug-induced inhibition of phosphorylation of STAT5 overrides drug resistance in neoplastic mast cells.Leukemia · 2018Article
- The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma.Veterinary and comparative oncology · 2018Article
- Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul That Continues Today.Frontiers in immunology · 2018Review
- The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part III: Polymorphisms of genes involved in Tregs' activation and function.Postepy dermatologii i alergologii · 2017Review
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
Recent data suggest that the signal transducer and activator of transcription (STAT)5 contributes to differentiation and growth of mast cells. It has also been described that constitutively phosphorylated STAT5 (pSTAT5) plays a pro-oncogenic role in various myeloid neoplasms. We examined the expression of pSTAT5 in neoplastic mast cells in systemic mastocytosis and asked whether the disease-related oncoprotein KIT D816V is involved in STAT5 activation. As assessed by immunohistochemistry using the anti-pSTAT5 antibody AX1, neoplastic mast cells were found to display pSTAT5 in all SM patients examined (n = 40). Expression of pSTAT5 was also demonstrable in the KIT D816V-positive mast cell leukemia cell line HMC-1. Using various staining-protocols, pSTAT5 was found to be located in both the cytoplasmic and nuclear compartment of mast cells. To define the functional role of KIT D816V in STAT5-activation, Ba/F3 cells with doxycycline-inducible expression of KIT D816V were used. In these cells, induction of KIT D816V resulted in an increased expression of pSTAT5 without substantial increase in total STAT5. Moreover, the KIT D816V-targeting kinase-inhibitor PKC412 was found to counteract expression of pSTAT5 in HMC-1 cells as well as doxycycline-induced expression of pSTAT5 in Ba/F3 cells. Finally, a dominant negative STAT5-construct was found to inhibit growth of HMC-1 cells. Together, our data show that neoplastic mast cells express cytoplasmic and nuclear pSTAT5, that KIT D816V promotes STAT5-activation, and that STAT5-activation contributes to growth of neoplastic mast cells.
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