Synergistic induction of PI-PLCΒ1 signaling by azacitidine and valproic acid in high-risk myelodysplastic syndromes

M. Y. Follo, C. Finelli, S. Mongiorgi, C. Clissa, F. Chiarini, G. Ramazzotti, S. Paolini, G. Martinelli, A. M. Martelli, L. Cocco

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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) Β1 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-PLCΒ1 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-PLCΒ1 expression in high-risk MDS patients. Furthermore, we observed an increase in Cyclin D3 expression, a downstream target of PI-PLCΒ1 signaling, therefore suggesting a potential combined activity of AZA and VPA in high-risk MDS in activating PI-PLCΒ1 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-PLCΒ1 signaling in the epigenetic therapy, which may also lead to the identification of innovative targets for the epigenetic therapy of high-risk MDS.

Original languageEnglish
Pages (from-to)271-280
Number of pages10
JournalLeukemia
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Azacitidine
Myelodysplastic Syndromes
Valproic Acid
Epigenomics
Cyclin D3
Phosphoinositide Phospholipase C
Therapeutics
Acute Myeloid Leukemia
Cell Differentiation
Cell Proliferation

Keywords

  • azacitidine
  • epigenetics
  • myelodysplastic syndromes
  • PI-PLCb1
  • valproic acid

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Follo, M. Y., Finelli, C., Mongiorgi, S., Clissa, C., Chiarini, F., Ramazzotti, G., ... Cocco, L. (2011). Synergistic induction of PI-PLCΒ1 signaling by azacitidine and valproic acid in high-risk myelodysplastic syndromes. Leukemia, 25(2), 271-280. https://doi.org/10.1038/leu.2010.266

Synergistic induction of PI-PLCΒ1 signaling by azacitidine and valproic acid in high-risk myelodysplastic syndromes. / Follo, M. Y.; Finelli, C.; Mongiorgi, S.; Clissa, C.; Chiarini, F.; Ramazzotti, G.; Paolini, S.; Martinelli, G.; Martelli, A. M.; Cocco, L.

In: Leukemia, Vol. 25, No. 2, 02.2011, p. 271-280.

Research output: Contribution to journalArticle

Follo, MY, Finelli, C, Mongiorgi, S, Clissa, C, Chiarini, F, Ramazzotti, G, Paolini, S, Martinelli, G, Martelli, AM & Cocco, L 2011, 'Synergistic induction of PI-PLCΒ1 signaling by azacitidine and valproic acid in high-risk myelodysplastic syndromes', Leukemia, vol. 25, no. 2, pp. 271-280. https://doi.org/10.1038/leu.2010.266
Follo, M. Y. ; Finelli, C. ; Mongiorgi, S. ; Clissa, C. ; Chiarini, F. ; Ramazzotti, G. ; Paolini, S. ; Martinelli, G. ; Martelli, A. M. ; Cocco, L. / Synergistic induction of PI-PLCΒ1 signaling by azacitidine and valproic acid in high-risk myelodysplastic syndromes. In: Leukemia. 2011 ; Vol. 25, No. 2. pp. 271-280.
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