Sézary 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 PTEN downregulation is observed in almost all of the samples evaluated by quantitative reverse-transcriptase polymerase chain reaction and Western blotting analysis. Neither DNA sequence mutation nor promoter hypermethylation were found at the 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, because reduced PTEN activates the PI3/AKT-mediated pathway of cell growth and survival, we demonstrate that PTEN deficiency is associated with activ
Comprehensive analysis of PTEN status in Sezary Syndrome / Cristofoletti, Cristina; Picchio, MARIA CRISTINA; Lazzeri, Cristina; Tocco, Valeria; Pagani, Elena; Bresin, Antonella; Mancini, Barbara; Passarelli, Francesca; Facchiano, Antonio; Scala, Enrico; Lombardo, Giuseppe Alfonso; Cantonetti, Maria; Caprini, Elisabetta; Russo, Giandomenico; Narducci, Maria Grazia. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 122:20(2013), pp. 1-25. [10.1182/blood-2013-06-510578]
Comprehensive analysis of PTEN status in Sezary Syndrome
CRISTOFOLETTI, CRISTINA;PICCHIO, MARIA CRISTINA;LAZZERI, CRISTINA;BRESIN, antonella;PASSARELLI, Francesca;SCALA, Enrico;
2013
Abstract
Sézary 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 PTEN downregulation is observed in almost all of the samples evaluated by quantitative reverse-transcriptase polymerase chain reaction and Western blotting analysis. Neither DNA sequence mutation nor promoter hypermethylation were found at the 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, because reduced PTEN activates the PI3/AKT-mediated pathway of cell growth and survival, we demonstrate that PTEN deficiency is associated with activI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
