An increased expression of PI-PLC beta 1 is associated with myeloid differentiation and a longer response to azacitidine in myelodysplastic syndromes

作者：Cocco Lucio; Finelli Carlo; Mongiorgi Sara; Clissa Cristina; Russo Domenico; Bosi Costanza; Quaranta Marilisa; Malagola Michele; Parisi Sarah; Stanzani Marta; Ramazzotti Giulia; Mariani Giulia A; Billi Anna Maria; Manzoli Lucia; Follo Matilde Y^*

来源：Journal of Leukocyte Biology, 2015, 98(5): 769-780.

DOI：10.1189/jlb.2MA1114-541R

• phospholipase C beta 1
• methylation
• gene expression
• hematological malignancies
• epigenetic therapy

This study tested the hypothesis that PI-PLC beta 1 is associated with myeloid differentiation and that its expression could be useful for predicting the response of MDS patients to azacitidine, as the clinical effect of epigenetic treatments is often detectable only after several cycles of therapy. To this end, PI-PLC beta 1 was quantified on 70 MDS patients (IPSS risk: 13 Low, 20 Int-1, 31 Int-2, 6 High) at baseline and during the first 3 cycles of azacitidine. Results were then compared with the hematologic response, as assessed after the sixth cycle of azacitidine therapy. Overall, 60 patients completed 6 cycles of azacitidine, and for them, a clinical and molecular evaluation was possible: 37 of these patients (62%) showed a specific increase of PI-PLC beta 1 mRNA within the first 3 cycles, which was associated with a longer duration of response and with an increased myeloid differentiation, as evidenced by PI-PLC gamma 2 induction and the recruitment of specific myeloid-associated transcription factors to the PI-PLC beta 1 promoter during azacitidine response. Moreover, the increase of cyclin D3 gene expression throughout all of the therapy showed that PI-PLC beta 1-dependent signaling is indeed activated in azacitidine responder patients. Taken together, our results show that PI-PLC beta 1 quantification in MDS predicts the response to azacitidine and is associated with an increased myeloid differentiation.

• 出版日期2015-11