Publications

Authors:

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

Title:

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

Year:

2020

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

CANCERS

ISSN of journal:

2072-6694

N° Volume:

12

Number or Folder:

3

Page numbers:

597-615

Keyword:

Bone Marrow Failure Syndromes; STAT3; lymphocytes; mTOR

Short description of contents:

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.

Product ID:

113744

Handle IRIS:

11562/1014603

Last Modified:

November 16, 2022

Bibliographic citation:

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

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