Format

Send to

Choose Destination
See comment in PubMed Commons below
J Clin Oncol. 2009 Feb 10;27(5):782-90. doi: 10.1200/JCO.2008.19.3748. Epub 2008 Dec 29.

Phosphoinositide-phospholipase C beta1 mono-allelic deletion is associated with myelodysplastic syndromes evolution into acute myeloid leukemia.

Author information

  • 1Department of Human Anatomical Sciences, Cellular Signalling Laboratory, University of Bologna, Bologna, Italy. lucio.cocco@unibo.it

Abstract

PURPOSE:

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.

CONCLUSION:

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.

PMID:
19114693
DOI:
10.1200/JCO.2008.19.3748
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon
    Loading ...
    Support Center