| Title: |
A miRNA screening identifies miR-192-5p as associated with response to azacitidine and lenalidomide therapy in myelodysplastic syndromes |
| Authors: |
Mongiorgi, Sara; De Stefano, Alessia; Ratti, Stefano; Indio, Valentina; Astolfi, Annalisa; Casalin, Irene; Pellagatti, Andrea; Paolini, Stefania; Parisi, Sarah; Cavo, Michele; Pession, Andrea; McCubrey, James A; Suh, Pann-Ghill; Manzoli, Lucia; Boultwood, Jacqueline; Finelli, Carlo; Cocco, Lucio; Follo, Matilde Y |
| Contributors: |
Mongiorgi, Sara; De Stefano, Alessia; Ratti, Stefano; Indio, Valentina; Astolfi, Annalisa; Casalin, Irene; Pellagatti, Andrea; Paolini, Stefania; Parisi, Sarah; Cavo, Michele; Pession, Andrea; McCubrey, James A; Suh, Pann-Ghill; Manzoli, Lucia; Boultwood, Jacqueline; Finelli, Carlo; Cocco, Lucio; Follo, Matilde Y |
| Publication Year: |
2023 |
| Collection: |
IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| Subject Terms: |
Azacitidine; BCL2; Lenalidomide; Myelodysplastic syndrome; miRNA profiling |
| Description: |
Background miRNAs are small non-coding RNAs that regulate gene expression and are linked to cancer development and progression. miRNA profiles are currently studied as new prognostic factors or therapeutic perspectives. Among hematological cancers, myelodysplastic syndromes at higher risk of evolution into acute myeloid leukemia are treated with hypomethylating agents, like azacitidine, alone or in combination with other drugs, such as lenalidomide. Recent data showed that, during azacitidine and lenalidomide therapy, the concurrent acquisition of specific point mutations affecting inositide signalling pathways is associated with lack or loss of response to therapy. As these molecules are implicated in epigenetic processes, possibly involving miRNA regulation, and in leukemic progression, through the regulation of proliferation, differentiation and apoptosis, here we performed a new miRNA expression analysis of 26 high-risk patients with myelodysplastic syndromes treated with azacitidine and lenalidomide at baseline and during therapy. miRNA array data were processed, and bioinformatic results were correlated with clinical outcome to investigate the translational relevance of selected miRNAs, while the relationship between selected miRNAs and specific molecules was experimentally tested and proven.Results Patients' overall response rate was 76.9% (20/26 cases): complete remission (5/26, 19.2%), partial remission (1/26, 3.8%), marrow complete remission (2/26, 7.7%), hematologic improvement (6/26, 23.1%), hematologic improvement with marrow complete remission (6/26, 23.1%), whereas 6/26 patients (23.1%) had a stable disease. miRNA paired analysis showed a statistically significant up-regulation of miR-192-5p after 4 cycles of therapy (vs baseline), that was confirmed by real-time PCR analyses, along with an involvement of BCL2, that was proven to be a miR-192-5p target in hematopoietic cells by luciferase assays. Furthermore, Kaplan-Meier analyses showed a significant correlation between high levels of miR-192-5p ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/36803590; info:eu-repo/semantics/altIdentifier/wos/WOS:000934593400002; volume:15; issue:1; firstpage:1; lastpage:12; numberofpages:12; journal:CLINICAL EPIGENETICS; https://hdl.handle.net/11585/932013 |
| DOI: |
10.1186/s13148-023-01441-9 |
| Availability: |
https://hdl.handle.net/11585/932013; https://doi.org/10.1186/s13148-023-01441-9; https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-023-01441-9 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.F7B32FC4 |
| Database: |
BASE |