ArticleNature communications2022
Discovery of a signaling feedback circuit that defines interferon responses in myeloproliferative neoplasms.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- The Dual Role of Interferon Signaling in Myeloproliferative Neoplasms: Pathogenesis and Targeted Therapeutics.Cancers · 2025Review
- Article
- 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
- Loss of Function Mouse Models Reveal a Novel Regulatory Function for ULK1 in Myeloproliferative Neoplasms.Molecular and cellular biology · 2025Article
- Physiological functions of ULK1/2.Journal of molecular biology · 2024Review
- Myeloproliferative Neoplasms: Contemporary Review and Molecular Landscape.International journal of molecular sciences · 2023Review
- Long-acting interferon: pioneering disease modification of myeloproliferative neoplasms.The Korean journal of internal medicine · 2023Review
- [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
- Article
- Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells.Cancer research communications · 2023Article
- Review
- Article
- Targeting ULK1 Decreases IFNγ-Mediated Resistance to Immune Checkpoint Inhibitors.Molecular cancer research : MCR · 2023Article
- Recent advances in therapies for primary myelofibrosis.Faculty reviews · 2023Review
- Paving the way to improve therapy for Myeloproliferative Neoplasms.Nature communications · 2022Article
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Interferons (IFNs) are key initiators and effectors of the immune response against malignant cells and also directly inhibit tumor growth. IFNα is highly effective in the treatment of myeloproliferative neoplasms (MPNs), but the mechanisms of action are unclear and it remains unknown why some patients respond to IFNα and others do not. Here, we identify and characterize a pathway involving PKCδ-dependent phosphorylation of ULK1 on serine residues 341 and 495, required for subsequent activation of p38 MAPK. We show that this pathway is essential for IFN-suppressive effects on primary malignant erythroid precursors from MPN patients, and that increased levels of ULK1 and p38 MAPK correlate with clinical response to IFNα therapy in these patients. We also demonstrate that IFNα treatment induces cleavage/activation of the ULK1-interacting ROCK1/2 proteins in vitro and in vivo, triggering a negative feedback loop that suppresses IFN responses. Overexpression of ROCK1/2 is seen in MPN patients and their genetic or pharmacological inhibition enhances IFN-anti-neoplastic responses in malignant erythroid precursors from MPN patients. These findings suggest the clinical potential of pharmacological inhibition of ROCK1/2 in combination with IFN-therapy for the treatment of MPNs.
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