Policitemia Vera: scoperta di saggi di biopsia liquida finalizzata a identificare i biomarcatori correlati al rischio trombotico - PhDData

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Policitemia Vera: scoperta di saggi di biopsia liquida finalizzata a identificare i biomarcatori correlati al rischio trombotico

The thesis was published by Auteri, Giuseppe <1988>, in June 2023, Universita di Bologna.

Abstract:

Polycythemia Vera (PV) is a myeloproliferative neoplasm with an increased risk of thrombosis and progression to Myelofibrosis. Chronic inflammation is commonly observed in myeloproliferative neoplasms, including PV. The inflammatory network, among other components, includes extracellular vesicles (EVs), which play a role in cell-cell communication. In addition, circulating microbial components have recently been indicated as potential modifiers of inflammation, coagulation and hematopoiesis in general.
Here we studied the microbial DNA of circulating EVs through.
Peripheral blood and feces were collected from patients with PV (n=38) and from healthy donors (n=30). Circulating EVs derived from megakaryocytes (MK) and platelets (PLT) were analyzed by flow cytometry. After extraction of microbial DNA from feces and isolated EVs, the V3-V4 region of 16S rDNA was sequenced.
The proportion of EVs from MK was reduced in patients with PV compared with healthy donors. In contrast, the proportion of EVs from PLT was increased. PV was also associated with a microbial DNA signature of the isolated EVs with higher diversity and distinct microbial composition compared with the healthy counterpart. There is a higher proportion of lipopolysaccharide-associated EVs in patients with PV. The gut microbiome profile did not differ between PV and doantors.
In addition, increased proportion of EVs of MK and decreased EVs of plates identified patients with previous thrombosis. EVs of patients with thrombosis were depleted in Staphylococcus DNA but enriched in Actinobacteria and Anaerococcus DNA. In addition, these patients had lower levels of lipopolysaccharide-associated EVs.
Patients with spinal cord fibrosis had a higher proportion of PE-EVs and were enriched in Collinsella and Flavobacterium DNA.
These data may help refine the prognosis of PV and identify new drug targets.



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