Phosphoinositide-Phospholipase C β1 Mono-Allelic Deletion Is Associated With Myelodysplastic Syndromes Evolution Into Acute Myeloid Leukemia

Purpose To evaluate the association between the presence of phosphoinositide-phospholipase C beta 1 (PI-PLC beta 1) mono-allelic deletion with the clinical outcome of myelodysplastic syndromes (MDS) patients. Methods PI-PLC beta 1, PI-PLC beta 4, and PI-PLC gamma 1 cytogenetic investigations were performed on 80 newly diagnosed MDS patients (18 low risk, 26 intermediate 1, 18 intermediate 2, 18 high risk) comparing the results with the clinical outcome of the patients. Moreover, fluorescent in situ hybridization results were validated by real-time polymerase chain reaction (PCR). Finally, PI-PLC beta 1 gene and protein expression were assessed by both real-time PCR and immunocytochemical experiments. Results Collectively, 35 (43.75%) of 80 of the MDS patients showed a specific mono-allelic deletion of PI-PLC beta 1. Kaplan-Meier analysis revealed a significant association (P < .0001) between the PI-PLC beta 1 mono-allelic deletion and a higher risk of evolution into acute myeloid leukemia (AML), since 23 of 35 MDS patients (65.7%) bearing the PI-PLC beta 1 mono-allelic deletion evolved into AML. Even in multivariate analysis, the PI-PLC beta 1 mono-allelic deletion retained a higher significance, with a P < .001, as a prognostic factor of evolution into AML (odds ratio [ OR] 1.83; 95% Cl, 2.26 to 17.24; P = .00045). Finally, PI-PLC beta 1 deletion was related to an altered gene and protein expression. Conclusion PI-PLC beta 1 mono-allelic deletion is associated with a worse clinical outcome in MDS patients, hinting at the identification of a new group at higher risk of AML evolution and representing a reliable prognostic tool. Moreover, targeting PI-PLC beta 1 pathways might emerge as a new therapeutic strategy for MDS.