ArticleLeukemia2019
Homomultimerization of mutant calreticulin is a prerequisite for MPL binding and activation.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- Mutant calreticulin-directed immunotherapies in myeloproliferative neoplasms.Blood neoplasia · 2026Review
- Loss of KDEL function from a calreticulin frameshift mutation drives expression of an immature, mutant calreticulin-dependent form of the thrombopoietin receptor MPL.Haematologica · 2026Article
- Novel strategies targeting mutant calreticulin in essential thrombocythemia and myelofibrosis.Blood · 2026Review
- Mutant calreticulin enables potent and selective CAR-T cell therapy in preclinical models of myeloproliferative neoplasms.Journal for immunotherapy of cancer · 2026Article
- Challenges in the Evolving Role of Calreticulin as a Promising Target for Precision Medicine in Myeloproliferative Neoplasms.Cancers · 2025Review
- Article
- Mutant Calreticulin in MPN: Mechanistic Insights and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
- Diagnosis- and Prognosis-Related Gene Alterations inInternational journal of molecular sciences · 2023Review
- Review
- Oncogenic CALR mutant C-terminus mediates dual binding to the thrombopoietin receptor triggering complex dimerization and activation.Nature communications · 2023Article
- Effects of calreticulin mutations on cell transformation and immunity.Journal of cellular and molecular medicine · 2023Review
- Human gene-engineered calreticulin mutant stem cells recapitulate MPN hallmarks and identify targetable vulnerabilities.Leukemia · 2023Article
- Structural and Dynamic Differences between Calreticulin Mutants Associated with Essential Thrombocythemia.Biomolecules · 2023Article
- Article
- A marine sponge-derived lectin reveals hidden pathway for thrombopoietin receptor activation.Nature communications · 2022Article
- Targeting human CALR-mutated MPN progenitors with a neoepitope-directed monoclonal antibody.EMBO reports · 2022Article
- The Response to Oxidative Damage Correlates with Driver Mutations and Clinical Outcome in Patients with Myelofibrosis.Antioxidants (Basel, Switzerland) · 2022Article
- CALR frameshift mutations in MPN patient-derived iPSCs accelerate maturation of megakaryocytes.Stem cell reports · 2021Article
- MPL overexpression induces a high level of mutant-CALR/MPL complex: a novel mechanism of ruxolitinib resistance in myeloproliferative neoplasms with CALR mutations.International journal of hematology · 2021Article
- In and out: Traffic and dynamics of thrombopoietin receptor.Journal of cellular and molecular medicine · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Studies have previously shown that mutant calreticulin (CALR), found in a subset of patients with myeloproliferative neoplasms (MPNs), interacts with and subsequently promotes the activation of the thrombopoietin receptor (MPL). However, the molecular mechanism behind the activity of mutant CALR remains unknown. Here we show that mutant, but not wild-type, CALR interacts to form a homomultimeric complex. This intermolecular interaction among mutant CALR proteins depends on their carboxyl-terminal domain, which is generated by a unique frameshift mutation found in patients with MPN. With a competition assay, we demonstrated that the formation of mutant CALR homomultimers is required for the binding and activation of MPL. Since association with MPL is required for the oncogenicity of mutant CALR, we propose a model in which the constitutive activation of the MPL downstream pathway by mutant CALR multimers induces the development of MPN. This study provides a potential novel therapeutic strategy against mutant CALR-dependent tumorigenesis via targeting the intermolecular interaction among mutant CALR proteins.
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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.