ArticleExperimental hematology2009
Polycythemia vera erythroid precursors exhibit increased proliferation and apoptosis resistance associated with abnormal RAS and PI3K pathway activation.
Article in Experimental hematology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 72 citations in OpenAlex.
- Network pharmacology-based analysis of the antithrombotic clinical efficacy and antithrombotic mechanism of Huoxue Jiedu prescription in the treatment of polycythemia vera with heat toxin and blood stasis syndrome.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Trial
- Metabolomic Profiling Reveals Distinct Signatures in Primary and Secondary Polycythemia.Metabolites · 2025Article
- Gadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms.Nature communications · 2024Article
- Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs.Journal of animal science and biotechnology · 2023Article
- Insights into the Potential Mechanisms of JAK2V617F Somatic Mutation Contributing Distinct Phenotypes in Myeloproliferative Neoplasms.International journal of molecular sciences · 2022Review
- ZDQ-0620, a Novel Phosphatidylinositol 3-Kinase Inhibitor, Inhibits Colorectal Carcinoma Cell Proliferation and Suppresses Angiogenesis by Attenuating PI3K/AKT/mTOR Pathway.Frontiers in oncology · 2022Article
- Review
- The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization.International journal of molecular sciences · 2021Review
- Recent Advances in the Use of Molecular Analyses to Inform the Diagnosis and Prognosis of Patients with Polycythaemia Vera.International journal of molecular sciences · 2021Review
- The extracellular signal-regulated kinase 1/2 modulates the intracellular localization of DNA methyltransferase 3A to regulate erythrocytic differentiation.American journal of translational research · 2020Article
- Effect of the conditional knockout of bone marrow specific RIPK3 gene on bone marrow hematopoiesis in mice.International journal of clinical and experimental pathology · 2018Article
- PI3K-Akt Signal Transduction Molecules Maybe Involved in Downregulation of Erythroblasts Apoptosis and Perifosine Increased Its Apoptosis in Chronic Mountain Sickness.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Review
- The role of glucocorticoid receptor (GR) polymorphisms in human erythropoiesis.American journal of blood research · 2014Article
- Molecular classification of myeloproliferative neoplasms-pros and cons.Current hematologic malignancy reports · 2013Review
- AKT is a therapeutic target in myeloproliferative neoplasms.Leukemia · 2013Article
- Article
- Targeting JAK2 in the therapy of myeloproliferative neoplasms.Expert opinion on therapeutic targets · 2012Review
- Article
- Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival.BMC cancer · 2011Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectivePolycythemia vera (PV) is characterized by erythrocytosis associated with the presence of the activating JAK2(V617F) mutation in a variable proportion of hematopoietic cells. JAK2(V617F) is detected in other myeloproliferative neoplasms, does not appear to be the PV-initiating event, and its specific role in deregulated erythropoiesis in PV is incompletely understood. We investigated the pathogenesis of PV to characterize abnormal proliferation and apoptosis responses and aberrant oncogenic pathway activation in primary PV erythroid precursors. MATERIALS AND
methodsPeripheral blood CD34(+) cells isolated from PV patients and healthy controls were grown in liquid culture to expand a population of primary erythroblasts for experiments designed to analyze cellular proliferation, apoptosis, JAK2(V617F) mutation status, cytokine-dependent protein phosphorylation and gene expression profiling using Affymetrix microarrays.
resultsThe survival and proliferation of PV erythroblasts were growth factor-dependent under strict serum-free conditions requiring both erythropoietin (EPO) and stem cell factor. PV erythroblasts exhibited EPO hypersensitivity and enhanced cellular proliferation associated with increased EPO-mediated extracellular signal-regulated kinases 1 and 2 phosphorylation. EPO-induced AKT phosphorylation was observed in PV but not normal erythroblasts, an effect associated with apoptosis resistance in PV erythroblasts. Analysis of gene expression and oncogenic pathway activation signatures revealed increased RAS (p<0.01) and phosphoinositide-3 kinase (p<0.05) pathway activation in PV erythroblasts.
conclusionDeregulated erythropoiesis in PV involves EPO hypersensitivity and apoptosis resistance of erythroid precursor cells associated with abnormally increased activation of RAS-ERK and phosphoinositide-3 kinase-AKT pathways. These data suggest that investigation of the mechanisms of abnormal RAS and phosphoinositide-3 kinase pathway activation in erythroblasts may contribute to our understanding of the molecular pathogenesis of PV.
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