Pubblicazioni

Autori:

Vella, Antonio; D'Aversa, Elisabetta; Api, Martina; Breveglieri, Giulia; Allegri, Marisole; Giacomazzi, Alice; Busilacchi, Elena Marinelli; Fabrizzi, Benedetta; Cestari, Tiziana; Sorio, Claudio; Bedini, Gloria; D'Amico, Giovanna; Bronte, Vincenzo; Poloni, Antonella; Benedetti, Antonio; Bovo, Chiara; Corey, Seth J; Borgatti, Monica; Cipolli, Marco; Bezzerri, Valentino

Titolo:

mTOR and STAT3 Pathway Hyper-Activation is Associated with evated Interleukin-6 Levels in Patients with Shwachman-Diamond Syndrome: Further Evidence of Lymphoid Lineage Impairment

Anno:

2020

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

Elettronico

Referee:

Sì

Nome rivista:

CANCERS

ISSN Rivista:

2072-6694

N° Volume:

12

Numero o Fascicolo:

3

Intervallo pagine:

597-615

Parole chiave:

Bone Marrow Failure Syndromes; STAT3; lymphocytes; mTOR

Breve descrizione dei contenuti:

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.

Id prodotto:

113744

Handle IRIS:

11562/1014603

ultima modifica:

16 novembre 2022

Citazione bibliografica:

Vella, Antonio; D'Aversa, Elisabetta; Api, Martina; Breveglieri, Giulia; Allegri, Marisole; Giacomazzi, Alice; Busilacchi, Elena Marinelli; Fabrizzi, Benedetta; Cestari, Tiziana; Sorio, Claudio; Bedini, Gloria; D'Amico, Giovanna; Bronte, Vincenzo; Poloni, Antonella; Benedetti, Antonio; Bovo, Chiara; Corey, Seth J; Borgatti, Monica; Cipolli, Marco; Bezzerri, Valentino, mTOR and STAT3 Pathway Hyper-Activation is Associated with evated Interleukin-6 Levels in Patients with Shwachman-Diamond Syndrome: Further Evidence of Lymphoid Lineage Impairment «CANCERS» , vol. 12 , n. 3 , 2020 , pp. 597-615

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo