title: Phosphoinositide-phospholipase C beta1 mono-allelic deletion is associated with myelodysplastic syndromes evolution into acute myeloid leukemia.
abstract: OBJECTIVE
  To evaluate the association between the presence of phosphoinositide-phospholipase C beta1 (PI-PLCbeta1) mono-allelic deletion with the clinical outcome of myelodysplastic syndromes (MDS) patients.
  
  
  METHODS
  PI-PLCbeta1, PI-PLCbeta4, and PI-PLCgamma1 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-PLCbeta1 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-PLCbeta1. Kaplan-Meier analysis revealed a significant association (P < .0001) between the PI-PLCbeta1 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-PLCbeta1 mono-allelic deletion evolved into AML. Even in multivariate analysis, the PI-PLCbeta1 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% CI, 2.26 to 17.24; P = .00045). Finally, PI-PLCbeta1 deletion was related to an altered gene and protein expression.
  
  
  CONCLUSIONS
  PI-PLCbeta1 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-PLCbeta1 pathways might emerge as a new therapeutic strategy for MDS.
authors.affiliation: Department of Human Anatomical Sciences, Cellular Signalling Laboratory, University of Bologna, Bologna, Italy. lucio.cocco@unibo.it
authors.forename: Matilde Y
authors.initials: MY
authors.lastname: Follo
authors.forename: Carlo
authors.initials: C
authors.lastname: Finelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Clissa
authors.forename: Sara
authors.initials: S
authors.lastname: Mongiorgi
authors.forename: Costanza
authors.initials: C
authors.lastname: Bosi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Lucia
authors.initials: L
authors.lastname: Manzoli
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Martelli
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000235:genetics* / Q000401:mortality; D054799:Phospholipase C beta / Q000235:genetics*; D051966:Phospholipase C gamma / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054799:Phospholipase C beta; D051966:Phospholipase C gamma