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Inflammatory profile of lower risk myelodysplastic syndromes

J. Topping, A. Taylor, F. Nadat, S. Crouch, A. Ibbotson, J. Čermák, A. Symeonidis, A. Tatic, S. Langemeijer, E. Hellström-Lindberg, D. Culligan, HG. Garelius, J. Ashcroft, E. Nga, J. Parker, S. Kolade, MF. McDermott, T. De Witte, D. Bowen, A....

. 2024 ; 205 (3) : 1044-1054. [pub] 20240521

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25004139

Grantová podpora
Kennedy Trust for Rheumatology Research
779295 EU 2020 Horizon
National Institute for Health Research
Leeds Biomedical Research Centre
Novartis Pharmacy B.V. Oncology Europe
Amgen Limited
Celgene International
Janssen Pharmaceutica
Takeda Pharmaceuticals International
A29685 Cancer Research UK - United Kingdom

The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patients with lower risk MDS in comparison to healthy controls and patients with defined autoinflammatory disorders (AIDs). The ASC/NLRP3 specks were significantly elevated in MDS patients compared to healthy controls (p < 0.001) and these levels were comparable to those found in patients with AIDs. The distribution of protein specks positive only for ASC was different to ASC/NLRP3 ones suggesting that other ASC-containing inflammasome complexes might be important in the pathogenesis of MDS. Patients with MDS-SLD had the lowest levels of interleukin (IL)-1β, tumour necrosis factor (TNF), IL-23, IL-33, interferon (IFN) γ and IFN-α2, compared to other diagnostic categories. We also found that inflammatory cytokine TNF was positively associated with MDS progression to a more aggressive form of disease and IL-6 and IL-1β with time to first red blood cell transfusion. Our study shows that there is value in analysing inflammatory biomarkers in MDS, but their diagnostic and prognostic utility is yet to be fully validated.

Citace poskytuje Crossref.org

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