ArticleLeukemia2017
A novel signalling screen demonstrates that CALR mutations activate essential MAPK signalling and facilitate megakaryocyte differentiation.
Article in Leukemia, 2017. 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, 63 citations in OpenAlex.
- Review
- CDK6 inactivation counteracts CALR-mutant-induced MPN evolution and sensitizes MPN stem cells to interferon-α treatment.HemaSphere · 2026Article
- Sabotaged Integral HSC Heterogeneity Underlies Essential Thrombocythemia Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mutant calreticulin enables potent and selective CAR-T cell therapy in preclinical models of myeloproliferative neoplasms.Journal for immunotherapy of cancer · 2026Article
- CALR Type 1-Like Mutations Increase Endoplasmic Reticulum Free CaCell biology international · 2025Article
- Hemoglobin-associatedFrontiers in medicine · 2025Article
- Article
- The Role of Mutated Calreticulin in the Pathogenesis ofInternational journal of molecular sciences · 2024Article
- Clonal evolution process from essential thrombocythemia to acute myeloid leukemia in the original patient from whom theNagoya journal of medical science · 2024Article
- Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer.Signal transduction and targeted therapy · 2023Review
- Transcriptomic Analysis Reveals JAK2/MPL-Independent Effects of Calreticulin Mutations in aCells · 2023Article
- JAK2V617F Mutant Megakaryocytes Contribute to Hematopoietic Aging in a Murine Model of Myeloproliferative Neoplasm.Stem cells (Dayton, Ohio) · 2022Article
- Megakaryocytes as the Regulator of the Hematopoietic Vascular Niche.Frontiers in oncology · 2022Review
- Conditional CRISPR-mediated deletion of Lyn kinase enhances differentiation and function of iPSC-derived megakaryocytes.Journal of thrombosis and haemostasis : JTH · 2022Article
- CALR frameshift mutations in MPN patient-derived iPSCs accelerate maturation of megakaryocytes.Stem cell reports · 2021Article
- Philadelphia-Negative MPN: A Molecular Journey, from Hematopoietic Stem Cell to Clinical Features.Medicina (Kaunas, Lithuania) · 2021Review
- High-throughput drug screening identifies the ATR-CHK1 pathway as a therapeutic vulnerability of CALR mutated hematopoietic cells.Blood cancer journal · 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
- Molecular pathogenesis of the myeloproliferative neoplasms.Journal of hematology & oncology · 2021Review
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Authors and funding
17 authors at 7 institutions in 1 country.
Funding
Abstract
Most myeloproliferative neoplasm (MPN) patients lacking JAK2 mutations harbour somatic CALR mutations that are thought to activate cytokine signalling although the mechanism is unclear. To identify kinases important for survival of CALR-mutant cells, we developed a novel strategy (KISMET) that utilizes the full range of kinase selectivity data available from each inhibitor and thus takes advantage of off-target noise that limits conventional small-interfering RNA or inhibitor screens. KISMET successfully identified known essential kinases in haematopoietic and non-haematopoietic cell lines and identified the mitogen activated protein kinase (MAPK) pathway as required for growth of the CALR-mutated MARIMO cells. Expression of mutant CALR in murine or human haematopoietic cell lines was accompanied by myeloproliferative leukemia protein (MPL)-dependent activation of MAPK signalling, and MPN patients with CALR mutations showed increased MAPK activity in CD34 cells, platelets and megakaryocytes. Although CALR mutations resulted in protein instability and proteosomal degradation, mutant CALR was able to enhance megakaryopoiesis and pro-platelet production from human CD34
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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.