ArticleCancers2020
mTOR and STAT3 Pathway Hyper-Activation is Associated with Elevated Interleukin-6 Levels in Patients with Shwachman-Diamond Syndrome: Further Evidence of Lymphoid Lineage Impairment.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Cytokine signaling pathway in cystic fibrosis: expression of SOCS and STATs genes in different clinical phenotypes of the disease.Molecular and cellular biochemistry · 2021Trial
- Beyond neutropenia: Immunological evaluation of patients with Shwachman-Diamond syndrome.British journal of haematology · 2026Article
- Ataluren improves hematopoietic and pancreatic disorders in Shwachman-Diamond syndrome patients: a compassionate program case-series.Nature communications · 2025Article
- Manganese mitigates atrazine-induced oxidative stress and hepatorenal toxicity: insights from network pharmacology and in vivo experimentation.BMC pharmacology & toxicology · 2025Article
- Decoding the anti-thrombotic effects of leonurine: a multimodal approach combining TCM repositioning and mTOR signaling.Chinese medicine · 2025Article
- mTORC1 and STAT3 signaling are indispensable for in vitro TGFβ1-dependent three-dimensional (3D) tendon constructs.BMB reports · 2025Article
- Inflammatory pathways and the bone marrow microenvironment in inherited bone marrow failure syndromes.Stem cells (Dayton, Ohio) · 2025Review
- The role of the tumour microenvironment in lung cancer and its therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Distinct peripheral pro-inflammatory profile associated with tuberous sclerosis complex and epilepsy.Epilepsia · 2025Article
- CKMT1B regulates the proliferation, migration, invasion, and apoptosis of colorectal cancer cells through the AKT/mTOR/STAT3 pathway.Molecular genetics and genomics : MGG · 2025Article
- Constitutive systemic inflammation in Shwachman-Diamond Syndrome.Molecular medicine (Cambridge, Mass.) · 2025Article
- Inactivation of ATG13 stimulates chronic demyelinating pathologies in muscle-serving nerves and spinal cord.Immunologic research · 2025Article
- Expression of JAK/STAT Signaling Proteins at Diagnosis and Remission in Patients with Acute Myeloid Leukemia.Oman medical journal · 2024Article
- The metabolic basis of inherited neutropenias.British journal of haematology · 2024Review
- Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants.Haematologica · 2023Article
- The Molecular and Genetic Mechanisms of Inherited Bone Marrow Failure Syndromes: The Role of Inflammatory Cytokines in Their Pathogenesis.Biomolecules · 2023Review
- Article
- Targeting STAT3 and STAT5 in Cancer.Cancers · 2020Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
Shwachman-Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome, resulting in neutropenia and a risk of myeloid neoplasia. A mutation in a ribosome maturation factor accounts for almost all of the cases. Lymphoid involvement in SDS has not been well characterized. We recently reported that lymphocyte subpopulations are reduced in SDS patients. We have also shown that the mTOR-STAT3 pathway is hyper-activated in SDS myeloid cell populations. Here we show that mTOR-STAT3 signaling is markedly upregulated in the lymphoid compartment of SDS patients. Furthermore, our data reveal elevated IL-6 levels in cellular supernatants obtained from lymphoblasts, bone marrow mononuclear and mesenchymal stromal cells, and plasma samples obtained from a cohort of 10 patients. Of note, everolimus-mediated inhibition of mTOR signaling is associated with basal state of phosphorylated STAT3. Finally, inhibition of mTOR-STAT3 pathway activation leads to normalization of IL-6 expression in SDS cells. Altogether, our data strengthen the hypothesis that SDS affects both lymphoid and myeloid blood compartment and suggest everolimus as a potential therapeutic agent to reduce excessive mTOR-STAT3 activation in SDS.
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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.