ArticleScientific reports2019
Calreticulin Ins5 and Del52 mutations impair unfolded protein and oxidative stress responses in K562 cells expressing CALR mutants.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Calreticulin Expression in Human Carcinomas: A Systematic Review and Meta-Analysis.Asian Pacific journal of cancer prevention : APJCP · 2023Pooled it
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- Gene Expression Analysis of Mitochondria-Associated Membrane (MAM)-Related Genes in ER Stress and Alzheimer's Disease.Cellular and molecular neurobiology · 2026Article
- Inhibition of calreticulin by protein nanoparticles carrying antisense oligonucleotides reduce gene expression and infection ofNanomedicine (London, England) · 2025Article
- Challenges in the Evolving Role of Calreticulin as a Promising Target for Precision Medicine in Myeloproliferative Neoplasms.Cancers · 2025Review
- CALR Type 1-Like Mutations Increase Endoplasmic Reticulum Free CaCell biology international · 2025Article
- Differential regulation of mTORC2 signalling by type I and type II calreticulin (CALR) driver mutations of myeloproliferative neoplasm.Cell communication and signaling : CCS · 2025Article
- New approaches to standard of care in early-phase myeloproliferative neoplasms: can interferon-α alter the natural history of the disease?Haematologica · 2025Review
- Chronic Inflammation in Primary Myelofibrosis: In-Depth Insights Into Pathogenesis and Promising Anti-Inflammatory Therapeutic Strategies.Mediators of inflammation · 2025Review
- Myeloproliferative Neoplasm-like Mutations of Calreticulin Induce Phenotypes Associated with Calreticulin Dysfunction inInternational journal of molecular sciences · 2024Article
- Article
- The Role of Mutated Calreticulin in the Pathogenesis ofInternational journal of molecular sciences · 2024Article
- Miltirone induces GSDME-dependent pyroptosis in colorectal cancer by activating caspase 3.Heliyon · 2024Article
- Assessment of Total Antioxidant Capacity, 8-Hydroxy-2'-deoxy-guanosine, the Genetic Landscape, and Their Associations inInternational journal of molecular sciences · 2024Article
- Neutrophil-specific expression of JAK2-V617F or CALRmut induces distinct inflammatory profiles in myeloproliferative neoplasia.Journal of hematology & oncology · 2024Article
- Calreticulin and JAK2V617F driver mutations induce distinct mitotic defects in myeloproliferative neoplasms.Scientific reports · 2024Article
- Proteogenetic drug response profiling elucidates targetable vulnerabilities of myelofibrosis.Nature communications · 2023Article
- ORM1 promotes tumor progression of kidney renal clear cell carcinoma (KIRC) through CALR-mediated apoptosis.Scientific reports · 2023Article
- Transcriptomic regulations of heat stress response in the liver of lactating dairy cows.BMC genomics · 2023Article
- Deficiency of miR-409-3p improves myocardial neovascularization and function through modulation of DNAJB9/p38 MAPK signaling.Molecular therapy. Nucleic acids · 2023Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Somatic mutations of calreticulin (CALR) have been described in approximately 60-80% of JAK2 and MPL unmutated Essential Thrombocythemia and Primary Myelofibrosis patients. CALR is an endoplasmic reticulum (ER) chaperone responsible for proper protein folding and calcium retention. Recent data demonstrated that the TPO receptor (MPL) is essential for the development of CALR mutant-driven Myeloproliferative Neoplasms (MPNs). However, the precise mechanism of action of CALR mutants haven't been fully unraveled. In this study, we showed that CALR mutants impair the ability to respond to the ER stress and reduce the activation of the pro-apoptotic pathway of the unfolded protein response (UPR). Moreover, our data demonstrated that CALR mutations induce increased sensitivity to oxidative stress, leading to increase oxidative DNA damage. We finally demonstrated that the downmodulation of OXR1 in CALR-mutated cells could be one of the molecular mechanisms responsible for the increased sensitivity to oxidative stress mediated by mutant CALR. Altogether, our data identify novel mechanisms collaborating with MPL activation in CALR-mediated cellular transformation. CALR mutants negatively impact on the capability of cells to respond to oxidative stress leading to genomic instability and on the ability to react to ER stress, causing resistance to UPR-induced apoptosis.
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