ArticleLeukemia2015
Protein kinase Cɛ inhibition restores megakaryocytic differentiation of hematopoietic progenitors from primary myelofibrosis patients.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Cytokine Landscapes, Immune Dysregulation, and Treatment Perspectives in Philadelphia-Negative Myeloproliferative Neoplasms: A Narrative Review.Journal of clinical medicine · 2025Review
- Associations of the circulating levels of cytokines with the risk of myeloproliferative neoplasms: a bidirectional mendelian-randomization study.BMC cancer · 2024Article
- Newly identified roles for PIEZO1 mechanosensor in controlling normal megakaryocyte development and in primary myelofibrosis.American journal of hematology · 2024Article
- Functionally Relevant Cytokine/Receptor Axes in Myelofibrosis.Biomedicines · 2023Review
- Interplay between Protein Kinase C Epsilon and Reactive Oxygen Species during Myogenic Differentiation.Cells · 2023Article
- SRSF2-P95H decreases JAK/STAT signaling in hematopoietic cells and delays myelofibrosis development in mice.Leukemia · 2023Article
- Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34Frontiers in oncology · 2022Article
- Megakaryocytes Are Regulators of the Tumor Microenvironment and Malignant Hematopoietic Progenitor Cells in Myelofibrosis.Frontiers in oncology · 2022Review
- Impact of the rs1024611 Polymorphism ofCancers · 2021Article
- A cancer-associated, genome protective programme engaging PKCε.Advances in biological regulation · 2020Review
- Review
- ROS in Platelet Biology: Functional Aspects and Methodological Insights.International journal of molecular sciences · 2020Review
- Article
- Protein Kinase C Epsilon Is a Key Regulator of Mitochondrial Redox Homeostasis in Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- PKCε Controls Mitotic Progression by Regulating Centrosome Migration and Mitotic Spindle Assembly.Molecular cancer research : MCR · 2018Article
- Platelet expression of PKCepsilon oncoprotein in myelofibrosis is associated with disease severity and thrombotic risk.Annals of translational medicine · 2017Article
- Human thrombopoiesis depends on Protein kinase Cδ/protein kinase Cε functional couple.Haematologica · 2016Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among the three classic Philadelphia chromosome-negative myeloproliferative neoplasms, primary myelofibrosis (PMF) is the most severe in terms of disease biology, survival and quality of life. Abnormalities in the process of differentiation of PMF megakaryocytes (MKs) are a hallmark of the disease. Nevertheless, the molecular events that lead to aberrant megakaryocytopoiesis have yet to be clarified. Protein kinase Cɛ (PKCɛ) is a novel serine/threonine kinase that is overexpressed in a variety of cancers, promoting aggressive phenotype, invasiveness and drug resistance. Our previous findings on the role of PKCɛ in normal (erythroid and megakaryocytic commitment) and malignant (acute myeloid leukemia) hematopoiesis prompted us to investigate whether it could be involved in the pathogenesis of PMF MK-impaired differentiation. We demonstrate that PMF megakaryocytic cultures express higher levels of PKCɛ than healthy donors, which correlate with higher disease burden but not with JAK2V617F mutation. Inhibition of PKCɛ function (by a negative regulator of PKCɛ translocation) or translation (by target small hairpin RNA) leads to reduction in PMF cell growth, restoration of PMF MK differentiation and inhibition of PKCɛ-related anti-apoptotic signaling (Bcl-xL). Our data suggest that targeting PKCɛ directly affects the PMF neoplastic clone and represent a proof-of-concept for PKCɛ inhibition as a novel therapeutic strategy in PMF.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.