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Synergistic induction of PI-PLCbeta1 signaling by azacitidine and valproic acid in high-risk myelodysplastic syndromes.

Authors: Follo, MY  Finelli, C  Mongiorgi, S  Clissa, C  Chiarini, F  Ramazzotti, G  Paolini, S  Martinelli, G  Martelli, AM  Cocco, L 
Citation: Follo MY, etal., Leukemia. 2011 Feb;25(2):271-80. doi: 10.1038/leu.2010.266. Epub 2010 Nov 26.
Pubmed: (View Article at PubMed) PMID:21109771
DOI: Full-text: DOI:10.1038/leu.2010.266

The association between azacitidine (AZA) and valproic acid (VPA) has shown high response rates in high-risk myelodysplastic syndromes (MDS) cases with unfavorable prognosis. However, little is known about the molecular mechanisms underlying this therapy, and molecular markers useful to monitor the disease and the effect of the treatment are needed. Phosphoinositide-phospholipase C (PI-PLC) beta1 is involved in both genetic and epigenetic mechanisms of MDS progression to acute myeloid leukemia. Indeed, AZA as a single agent was able to induce PI-PLCbeta1 expression, therefore providing a promising new tool in the evaluation of response to demethylating therapies. In this study, we assessed the efficacy of the combination of AZA and VPA on inducing PI-PLCbeta1 expression in high-risk MDS patients. Furthermore, we observed an increase in Cyclin D3 expression, a downstream target of PI-PLCbeta1 signaling, therefore suggesting a potential combined activity of AZA and VPA in high-risk MDS in activating PI-PLCbeta1 signaling, thus affecting cell proliferation and differentiation. Taken together, our findings might open up new lines of investigations aiming at evaluating the role of the activation of PI-PLCbeta1 signaling in the epigenetic therapy, which may also lead to the identification of innovative targets for the epigenetic therapy of high-risk MDS.

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CRRD Object Information
CRRD ID: 11535956
Created: 2016-09-23
Species: All species
Last Modified: 2016-09-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.