ArticleStem cell reports2021
CALR frameshift mutations in MPN patient-derived iPSCs accelerate maturation of megakaryocytes.
Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Immunogenetic and Transcriptomic Evidence Implicating the NKG2D-MICA/MICB Axis in CALR-Mutated Myeloproliferative Neoplasms.Cancers · 2026Article
- Protocol for generating megakaryocytes from patient induced pluripotent stem cells for disease modeling and compound screening.STAR protocols · 2026Article
- Plasma cfDNA and peripheral blood gDNA provide complementary information for molecular monitoring in myeloproliferative neoplasms.Frontiers in oncology · 2026Article
- 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
- Understanding Human Oncogene Function and Cooperativity in Myeloid Malignancy Using iPSCs.Experimental hematology · 2025Review
- Oncogenic Calreticulin Induces Immune Escape by Stimulating TGFβ Expression and Regulatory T-cell Expansion in the Bone Marrow Microenvironment.Cancer research · 2024Article
- Proinflammatory phenotype of iPS cell-derived JAK2 V617F megakaryocytes induces fibrosis in 3D in vitro bone marrow niche.Stem cell reports · 2024Article
- Non-canonical Hedgehog signaling mediates profibrotic hematopoiesis-stroma crosstalk in myeloproliferative neoplasms.Cell reports · 2024Article
- Development of a prognostic model to predict BLCA based on anoikis-related gene signature: preliminary findings.BMC urology · 2023Article
- KIT D816V Mast Cells Derived from Induced Pluripotent Stem Cells Recapitulate Systemic Mastocytosis Transcriptional Profile.International journal of molecular sciences · 2023Article
- The telomerase inhibitor imetelstat differentially targets JAK2V617F versus CALR mutant myeloproliferative neoplasm cells and inhibits JAK-STAT signaling.Frontiers in oncology · 2023Article
- Clonogenic assays improve determination of variant allele frequency of driver mutations in myeloproliferative neoplasms.Annals of hematology · 2022Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calreticulin (CALR) mutations are driver mutations in myeloproliferative neoplasms (MPNs), leading to activation of the thrombopoietin receptor and causing abnormal megakaryopoiesis. Here, we generated patient-derived CALRins5- or CALRdel52-positive induced pluripotent stem cells (iPSCs) to establish an MPN disease model for molecular and mechanistic studies. We demonstrated myeloperoxidase deficiency in granulocytic cells derived from homozygous CALR mutant iPSCs, rescued by repairing the mutation using CRISPR/Cas9. iPSC-derived megakaryocytes showed characteristics of primary megakaryocytes such as formation of demarcation membrane system and cytoplasmic pro-platelet protrusions. Importantly, CALR mutations led to enhanced megakaryopoiesis and accelerated megakaryocytic development in a thrombopoietin-independent manner. Mechanistically, our study identified differentially regulated pathways in mutated versus unmutated megakaryocytes, such as hypoxia signaling, which represents a potential target for therapeutic intervention. Altogether, we demonstrate key aspects of mutated CALR-driven pathogenesis dependent on its zygosity, and found novel therapeutic targets, making our model a valuable tool for clinical drug screening in MPNs.
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