ArticleOncogene2016
JAK2V617F mediates resistance to DNA damage-induced apoptosis by modulating FOXO3A localization and Bcl-xL deamidation.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Overexpression of FoxO3a in the dentate gyrus alleviates CUS-induced anxiety- and depression-like behaviors and cognitive impairment.Behavioral and brain functions : BBF · 2026Article
- Malignant JAK-signaling: at the interface of inflammation and malignant transformation.Leukemia · 2025Review
- Combined PARP inhibitors and small molecular inhibitors in solid tumor treatment (Review).International journal of oncology · 2023Review
- JAK2-Mediated Phosphorylation of Stress-Induced Phosphoprotein-1 (STIP1) in Human Cells.International journal of molecular sciences · 2022Article
- Acetylshikonin, A Novel CYP2J2 Inhibitor, Induces Apoptosis in RCC Cells via FOXO3 Activation and ROS Elevation.Oxidative medicine and cellular longevity · 2022Article
- Deletion of miR-451 curbs JAK2(V617F)-induced erythrocytosis in polycythemia vera by oxidative stress-mediated erythroblast apoptosis and hemolysis.Haematologica · 2020Article
- Inflammation exerts a nonrandom risk in the acquisition and progression of the MPN: Insights from a Mendelian randomization study.EClinicalMedicine · 2020Article
- Hypoxia-inducible factor 1 (HIF-1) is a new therapeutic target in JAK2V617F-positive myeloproliferative neoplasms.Leukemia · 2020Article
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- The ruxolitinib effect: understanding how molecular pathogenesis and epigenetic dysregulation impact therapeutic efficacy in myeloproliferative neoplasms.Journal of translational medicine · 2018Review
- Mutation landscape in patients with myelofibrosis receiving ruxolitinib or hydroxyurea.Blood cancer journal · 2018Article
- Amiodarone-Induced Retinal Neuronal Cell Apoptosis Attenuated by IGF-1 via Counter Regulation of the PI3k/Akt/FoxO3a Pathway.Molecular neurobiology · 2017Article
- FOXO3 Transcription Factor Is Essential for Protecting Hematopoietic Stem and Progenitor Cells from Oxidative DNA Damage.The Journal of biological chemistry · 2017Article
- Molecular determinants of pathogenesis and clinical phenotype in myeloproliferative neoplasms.Haematologica · 2017Review
- Evidence for AKT-independent regulation of FOXO1 and FOXO3 in haematopoietic stem and progenitor cells.Cell cycle (Georgetown, Tex.) · 2016Article
- Histone H2AX Is Involved in FoxO3a-Mediated Transcriptional Responses to Ionizing Radiation to Maintain Genome Stability.International journal of molecular sciences · 2015Article
- Reactive oxygen species overload promotes apoptosis in JAK2V617F-positive cell lines.Revista brasileira de hematologia e hemoterapiaArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The JAK2V617F mutation is found in most patients with a myeloproliferative neoplasm (MPN). This gain-of-function mutation dysregulates cytokine signaling and is associated with increased accumulation of DNA damage, a process likely to drive disease evolution. JAK2V617F inhibits NHE-1 upregulation in response to DNA damage and consequently represses Bcl-xL deamidation and apoptosis, thus giving rise to inappropriate cell survival. However, the mechanism whereby NHE-1 expression is inhibited by JAK2V617F is unknown. In this study, we demonstrate that the accumulation of reactive oxygen species (ROS) in cells expressing JAK2V617F compromises the NHE-1/Bcl-xL deamidation pathway by repressing NHE-1 upregulation in response to DNA damage. In JAK2V617F-positive cells, increased ROS levels results from aberrant PI3K signaling, which decreases nuclear localization of FOXO3A and decreases catalase expression. Furthermore, when compared with autologous control erythroblasts, clonally derived JAK2V617F-positive erythroblasts from MPN patients displayed increased ROS levels and reduced nuclear FOXO3A. However, in hematopoietic stem cells (HSCs), FOXO3A is largely localized within the nuclei despite the presence of JAK2V617F mutation, suggesting that JAK2-FOXO signaling has a different effect on progenitors compared with stem cells. Inactivation of FOXO proteins and elevation of intracellular ROS are characteristics common to many cancers, and hence these findings are likely to be of relevance beyond the MPN field.
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Registered trials
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