ArticleLeukemia2017
Calreticulin mutant mice develop essential thrombocythemia that is ameliorated by the JAK inhibitor ruxolitinib.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 71 citations in OpenAlex.
- Review
- 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
- Clonal hematopoiesis and hematological malignancy.The Journal of clinical investigation · 2024Review
- Lysosomal degradation targets mutant calreticulin and the thrombopoietin receptor in myeloproliferative neoplasms.Blood advances · 2024Article
- Proteogenetic drug response profiling elucidates targetable vulnerabilities of myelofibrosis.Nature communications · 2023Article
- Calreticulin as a marker and therapeutic target for cancer.Clinical and experimental medicine · 2023Review
- Human gene-engineered calreticulin mutant stem cells recapitulate MPN hallmarks and identify targetable vulnerabilities.Leukemia · 2023Article
- Effects of calreticulin mutations on cell transformation and immunity.Journal of cellular and molecular medicine · 2023Review
- A marine sponge-derived lectin reveals hidden pathway for thrombopoietin receptor activation.Nature communications · 2022Article
- Combined treatment of graft versus host disease using donor regulatory T cells and ruxolitinib.Scientific reports · 2022Article
- 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
- Mechanism of mutant calreticulin-mediated activation of the thrombopoietin receptor in cancers.The Journal of cell biology · 2021Article
- Induced Pluripotent Stem Cells Enable Disease Modeling and Drug Screening in Calreticulin del52 and ins5 Myeloproliferative Neoplasms.HemaSphere · 2021Article
- Calreticulin and cancer.Cell research · 2021Review
- Murine Models of Myelofibrosis.Cancers · 2020Review
- Mechanism underlying the development of myeloproliferative neoplasms through mutant calreticulin.Cancer science · 2020Review
- Article
- Different impact of calreticulin mutations on human hematopoiesis in myeloproliferative neoplasms.Oncogene · 2020Article
- Enhanced engraftment of human myelofibrosis stem and progenitor cells in MISTRG mice.Blood advances · 2020Article
Corrections and comments
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Authors and funding
23 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations of calreticulin (CALR) are detected in 25-30% of patients with essential thrombocythemia (ET) or primary myelofibrosis and cause frameshifts that result in proteins with a novel C-terminal. We demonstrate that CALR mutations activated signal transducer and activator of transcription 5 (STAT5) in 293T cells in the presence of thrombopoietin receptor (MPL). Human megakaryocytic CMK11-5 cells and erythroleukemic F-36P-MPL cells with knocked-in CALR mutations showed increased growth and acquisition of cytokine-independent growth, respectively, accompanied by STAT5 phosphorylation. Transgenic mice expressing a human CALR mutation with a 52 bp deletion (CALRdel52-transgenic mice (TG)) developed ET, with an increase in platelet count, but not hemoglobin level or white blood cell count, in association with an increase in bone marrow (BM) mature megakaryocytes. CALRdel52 BM cells did not drive away wild-type (WT) BM cells in in vivo competitive serial transplantation assays, suggesting that the self-renewal capacity of CALRdel52 hematopoietic stem cells (HSCs) was comparable to that of WT HSCs. Therapy with the Janus kinase (JAK) inhibitor ruxolitinib ameliorated the thrombocytosis in TG mice and attenuated the increase in number of BM megakaryocytes and HSCs. Taken together, our study provides a model showing that the C-terminal of mutant CALR activated JAK-STAT signaling specifically downstream of MPL and may have a central role in CALR-induced myeloproliferative neoplasms.
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