ArticleBlood2020
Defective interaction of mutant calreticulin and SOCE in megakaryocytes from patients with myeloproliferative neoplasms.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 76 citations in OpenAlex.
- Thermo-Chemically Modified Silk Scaffolds Reveal Niche-Driven Regulation of Hematopoiesis and Fibrosis.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- ER-associated degradation pathway protein SEL1L plays an evolutionarily conserved role in platelet adhesion.The Journal of clinical investigation · 2026Article
- Sabotaged Integral HSC Heterogeneity Underlies Essential Thrombocythemia Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular and Functional Analysis of Calcium Binding by a Cancer-linked Calreticulin Mutant.bioRxiv : the preprint server for biology · 2025Article
- α-Actinin-1 in Megakaryocytes: Its Structure, Interacting Proteins and Implications for Thrombopoiesis.Biomedicines · 2025Review
- Optogenetic induction of subcellular CaCommunications biology · 2025Article
- CALR Type 1-Like Mutations Increase Endoplasmic Reticulum Free CaCell biology international · 2025Article
- [The role of AKT inhibitors combined with Ruxolitinib in ameliorating myeloproliferative disorders in mice with CALR gene mutations].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Myeloproliferative Neoplasm-like Mutations of Calreticulin Induce Phenotypes Associated with Calreticulin Dysfunction inInternational journal of molecular sciences · 2024Article
- Versatility of megakaryocytes in homeostasis and disease.Blood science (Baltimore, Md.) · 2024Review
- Article
- Neutrophil-specific expression of JAK2-V617F or CALRmut induces distinct inflammatory profiles in myeloproliferative neoplasia.Journal of hematology & oncology · 2024Article
- Enkurin: a novel marker for myeloproliferative neoplasms from platelet, megakaryocyte, and whole blood specimens.Blood advances · 2023Article
- Calreticulin as a marker and therapeutic target for cancer.Clinical and experimental medicine · 2023Review
- Endoplasmic reticulum protein 5 attenuates platelet endoplasmic reticulum stress and secretion in a mouse model.Blood advances · 2023Article
- Inside-to-outside and back to the future of megakaryopoiesis.Research and practice in thrombosis and haemostasis · 2023Article
- Effects of calreticulin mutations on cell transformation and immunity.Journal of cellular and molecular medicine · 2023Review
- The Molecular Heterogeneity of Store-Operated CaInternational journal of molecular sciences · 2023Review
- Enkurin: A novel marker for myeloproliferative neoplasms from platelet, megakaryocyte, and whole blood specimens.bioRxiv : the preprint server for biology · 2023Article
- Recent advances in therapies for primary myelofibrosis.Faculty reviews · 2023Review
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
Approximately one-fourth of patients with essential thrombocythemia or primary myelofibrosis carry a somatic mutation of the calreticulin gene (CALR), the gene encoding for calreticulin. A 52-bp deletion (type I mutation) and a 5-bp insertion (type II mutation) are the most frequent genetic lesions. The mechanism(s) by which a CALR mutation leads to a myeloproliferative phenotype has been clarified only in part. We studied the interaction between calreticulin and store-operated calcium (Ca2+) entry (SOCE) machinery in megakaryocytes (Mks) from healthy individuals and from patients with CALR-mutated myeloproliferative neoplasms (MPNs). In Mks from healthy subjects, binding of recombinant human thrombopoietin to c-Mpl induced the activation of signal transducer and activator of transcription 5, AKT, and extracellular signal-regulated kinase 1/2, determining inositol triphosphate-dependent Ca2+ release from the endoplasmic reticulum (ER). This resulted in the dissociation of the ER protein 57 (ERp57)-mediated complex between calreticulin and stromal interaction molecule 1 (STIM1), a protein of the SOCE machinery that leads to Ca2+ mobilization. In Mks from patients with CALR-mutated MPNs, defective interactions between mutant calreticulin, ERp57, and STIM1 activated SOCE and generated spontaneous cytosolic Ca2+ flows. In turn, this resulted in abnormal Mk proliferation that was reverted using a specific SOCE inhibitor. In summary, the abnormal SOCE regulation of Ca2+ flows in Mks contributes to the pathophysiology of CALR-mutated MPNs. In perspective, SOCE may represent a new therapeutic target to counteract Mk proliferation and its clinical consequences in MPNs.
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