ArticleJournal of hematology & oncology2019
Differential roles of STAT1 and STAT2 in the sensitivity of JAK2V617F- vs. BCR-ABL-positive cells to interferon alpha.
Article in Journal of hematology & oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Nuclear adenomatous polyposis coli elevates STAT1 and reduces CXCL1,2, and 3 expression and inhibits neutrophil recruitment.Cellular signalling · 2025Article
- SARS-CoV-2 infection of human cortical cells is influenced by the interaction between aneuploidy and biological sex: insights from a Down syndrome in vitro model.Acta neuropathologica · 2025Article
- CRISPR/Cas9-Based Modeling ofInternational journal of molecular sciences · 2025Article
- Deciphering the complex clonal heterogeneity of polycythemia vera and the response to interferon alfa.Blood advances · 2025Article
- Integrating bulk RNA-seq and scRNA-seq data to explore diverse cell death patterns and develop a programmed cell death-related relapse prediction model in pediatric B-ALL.Scientific reports · 2025Article
- Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine IFNα and is enhanced by CD47 blockade.Scientific reports · 2025Article
- Cell Adhesion and Local Cytokine Control on Protein-Functionalized PNIPAM-co-AAc Hydrogel Microcarriers.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- 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
- The telomerase inhibitor imetelstat differentially targets JAK2V617F versus CALR mutant myeloproliferative neoplasm cells and inhibits JAK-STAT signaling.Frontiers in oncology · 2023Article
- Article
- Cellular and Molecular Mechanisms Involved in Hematopoietic Stem Cell Aging as a Clinical Prospect.Oxidative medicine and cellular longevity · 2022Review
- Expression profiles analysis identifies specific interferon-stimulated signatures as potential diagnostic and predictive indicators ofFrontiers in genetics · 2022Article
- Distinct effects of V617F and exon12-mutated JAK2 expressions on erythropoiesis in a human induced pluripotent stem cell (iPSC)-based model.Scientific reports · 2021Article
- Role of Inflammatory Factors during Disease Pathogenesis and Stem Cell Transplantation in Myeloproliferative Neoplasms.Cancers · 2020Review
- Mechanisms and rejuvenation strategies for aged hematopoietic stem cells.Journal of hematology & oncology · 2020Review
- Downregulation of RIG-I mediated by ITGB3/c-SRC/STAT3 signaling confers resistance to interferon-α-induced apoptosis in tumor-repopulating cells of melanoma.Journal for immunotherapy of cancer · 2020Article
- Bioinformatics Analysis of Key Genes and Pathways Associated with Thrombosis in Essential Thrombocythemia.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
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
backgroundInterferon alpha (IFNa) monotherapy is recommended as the standard therapy in polycythemia vera (PV) but not in chronic myeloid leukemia (CML). Here, we investigated the mechanisms of IFNa efficacy in JAK2V617F- vs. BCR-ABL-positive cells.
methodsGene expression microarrays and RT-qPCR of PV vs. CML patient PBMCs and CD34+ cells and of the murine cell line 32D expressing JAK2V617F or BCR-ABL were used to analyze and compare interferon-stimulated gene (ISG) expression. Furthermore, using CRISPR/Cas9n technology, targeted disruption of STAT1 or STAT2, respectively, was performed in 32D-BCR-ABL and 32D-JAK2V617F cells to evaluate the role of these transcription factors for IFNa efficacy. The knockout cell lines were reconstituted with STAT1, STAT2, STAT1Y701F, or STAT2Y689F to analyze the importance of wild-type and phosphomutant STATs for the IFNa response. ChIP-seq and ChIP were performed to correlate histone marks with ISG expression.
resultsMicroarray analysis and RT-qPCR revealed significant upregulation of ISGs in 32D-JAK2V617F but downregulation in 32D-BCR-ABL cells, and these effects were reversed by tyrosine kinase inhibitor (TKI) treatment. Similar expression patterns were confirmed in human cell lines, primary PV and CML patient PBMCs and CD34+ cells, demonstrating that these effects are operational in patients. IFNa treatment increased Stat1, Stat2, and Irf9 mRNA as well as pY-STAT1 in all cell lines; however, viability was specifically decreased in 32D-JAK2V617F. STAT1 or STAT2 knockout and reconstitution with wild-type or phospho-deficient STAT mutants demonstrated the necessity of STAT2 for IFNa-induced STAT1 phosphorylation in BCR-ABL- but not in JAK2V617F-expressing cells. STAT1 was essential for IFNa activity in both BCR-ABL- and JAK2V617F-positive cells. Furthermore, ChIP experiments demonstrate higher repressive and lower active chromatin marks at the promoters of ISGs in BCR-ABL-expressing cells.
conclusionsJAK2V617F but not BCR-ABL sensitizes MPN cells to interferon, and this effect was dependent on STAT1. Moreover, STAT2 is a survival factor in BCR-ABL- and JAK2V617F-positive cells but an IFNa-sensitizing factor solely in 32D-JAK2V617F cells by upregulation of STAT1 expression.
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