Cristofoletti C.,Istituto Dermopatico DellImmacolata Istituto di Ricovero e Cura rattere Scientifico |
Picchio M.C.,Istituto Dermopatico DellImmacolata Istituto di Ricovero e Cura rattere Scientifico |
Lazzeri C.,Istituto Dermopatico DellImmacolata Istituto di Ricovero e Cura rattere Scientifico |
Lazzeri C.,University of Rome La Sapienza |
And 12 more authors.
Blood | Year: 2013
Sezary syndrome (SS) is an incurable leukemic variant of cutaneous-T-cell lymphoma characterized by recurrent chromosomal alterations, among which, chromosome 10q deletion is very frequent. In this study, we investigated the PTEN status, on locus 10q23, in 44 SS patients; our findings show that PTEN is deleted in 36% of SS cases whereas a PTEN downregulation is observed in almost the totality of the samples evaluated by Quantitative RT-PCR and Western blotting analysis. Neither DNA sequence mutation nor promoter hypermethylation were found at PTEN locus, but we demonstrate that PTEN level can be also reduced by a group of miRs, previously found upregulated and of prognostic relevance in SS; particularly, miR-21, miR-106b and miR-486 were able to control PTEN abundance either in vitro or in vivo. Finally, since reduced PTEN activates the PI3/AKT mediated pathway of cell growth and survival, we demonstrate that PTEN deficiency is associated with activated AKT in skin resident but not in circulating SS cells suggesting that cutaneous milieu may strongly contribute to the SS cell growth. To our knowledge this is the first study fully exploring the PTEN status in a large cohort of SS patients unveiling potential elements of clinical utility in this malignancy.