ArticleLeukemia2019
JAK2V617F but not CALR mutations confer increased molecular responses to interferon-α via JAK1/STAT1 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 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Clinical outcomes of interferon therapy for polycythemia vera and essential thrombocythemia: a systematic review and meta-analysis.International journal of hematology · 2021Pooled it
- Genomic profiling of a randomized trial of interferon-α vs hydroxyurea in MPN reveals mutation-specific responses.Blood advances · 2022Trial
- Article
- Type 1 interferon perturbates clonal competition by reshaping human blood development.Nature genetics · 2026Article
- CDK6 inactivation counteracts CALR-mutant-induced MPN evolution and sensitizes MPN stem cells to interferon-α treatment.HemaSphere · 2026Article
- Novel strategies targeting mutant calreticulin in essential thrombocythemia and myelofibrosis.Blood · 2026Review
- Rapid Hematological and Molecular Response to Pegylated Interferon in WHO-Defined Pre-Fibrotic Myelofibrosis.Cancers · 2025Article
- NLRP3-induced systemic inflammation controls the development of JAK2V617F mutant myeloproliferative neoplasms.Nature communications · 2025Article
- Challenges in the Evolving Role of Calreticulin as a Promising Target for Precision Medicine in Myeloproliferative Neoplasms.Cancers · 2025Review
- Deciphering the complex clonal heterogeneity of polycythemia vera and the response to interferon alfa.Blood advances · 2025Article
- New approaches to standard of care in early-phase myeloproliferative neoplasms: can interferon-α alter the natural history of the disease?Haematologica · 2025Review
- Mutant Calreticulin in MPN: Mechanistic Insights and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
- STK405759 targets microtubules, modulates STAT1, and enhances ruxolitinib efficacy in myeloproliferative neoplasms.American journal of cancer research · 2025Article
- Myeloproliferative neoplasms in the adolescent and young adult population: A comprehensive review of the literature.British journal of haematology · 2024Review
- Drug Repositioning via Graph Neural Networks: Identifying Novel JAK2 Inhibitors from FDA-Approved Drugs through Molecular Docking and Biological Validation.Molecules (Basel, Switzerland) · 2024Article
- Calreticulin and JAK2V617F driver mutations induce distinct mitotic defects in myeloproliferative neoplasms.Scientific reports · 2024Article
- Upregulated SPAG6 correlates with increased STAT1 and is associated with reduced sensitivity of interferon-α response in BCR::ABL1 negative myeloproliferative neoplasms.Cancer science · 2023Article
- [Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
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Authors and funding
27 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pegylated interferon-α (peg-IFNa) treatment induces molecular responses (MR) in patients with myeloproliferative neoplasms (MPNs), including partial MR (PMR) in 30-40% of patients. Here, we compared the efficacy of IFNa treatment in JAK2V617F- vs. calreticulin (CALR)-mutated cells and investigated the mechanisms of differential response. Retrospective analysis of MPN patients treated with peg-IFNa demonstrated that patients harboring the JAK2V617F mutation were more likely to achieve PMR than those with mutated CALR (p = 0.004), while there was no significant difference in hematological response. In vitro experiments confirmed an upregulation of IFN-stimulated genes in JAK2V617F-positive 32D cells as well as patient samples (peripheral blood mononuclear cells and CD34+ hematopoietic stem cells) compared to their CALR-mutated counterparts, and higher IFNa doses were needed to achieve the same IFNa response in CALR- as in JAK2V617F-mutant 32D cells. Additionally, Janus-activated kinase-1 (JAK1) and signal transducers and activators of transcription 1 (STAT1) showed constitutive phosphorylation in JAK2V617F-mutated but not CALR-mutated cells, indicating priming towards an IFNa response. Moreover, IFN-induced growth arrest was counteracted by selective JAK1 inhibition but enhanced by JAK2 inhibition. In conclusion, our data suggest that, clinically, higher doses of IFNa are needed in CALR-mutated vs. JAK2V617F-positive patients and we suggest a model of JAK2V617F-JAK1/STAT1 crosstalk leading to a priming of JAK2V617F-positive cells to IFNa resulting in differential sensitivity.
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