23368

PPP1R13B

ASPP1|p53BP2-like|p85;protein phosphatase 1, regulatory subunit 13B;PPP1R13B;protein phosphatase 1, regulatory subunit 13B

apoptosis-stimulating of p53 protein 1|apoptosis-stimulating protein of p53, 1|protein phosphatase 1 regulatory subunit 13B|protein phosphatase 1, regulatory (inhibitor) subunit 13B

14q32.33

protein-coding

We have analyzed the regulation and expression of ASPP members, genes implicatedin the regulation of the apoptotic function of the TP53 tumor-suppressor gene, in acute lymphoblastic leukemia (ALL). expression of ASPP1 was significantly reduced in ALL and was dependent on hypermethylation of the ASPP1 gene promoter. Abnormal ASPP1 expression was associated with normal function of the tumor-suppressor gene TP53 in ALL. The analyses of 180 patients with ALL at diagnosis showed that the ASPP1 promoter was hypermethylated in 25% of cases with decreased mRNA expression. Methylation was significantly higher in adult ALL vs childhood ALL (32 vs 17%, P = 0.03) and T-ALL vs B-ALL (50 vs 9%, P = 0.001). Relapse rate (62vs 44%, P = 0.05) and mortality (59 vs 43%, P = 0.05) were significantly higher in patients with methylated ASPP1. DFS and OS were 32.8 and 33.7% for patients with unmethylated ASPP1 and 6.1 and 9.9% for methylated patients (P < 0.001 y P < 0.02, respectively). On the multivariate analysis, methylation of the ASPP1 genepromoter was an independent poor prognosis factor in ALL patients. Our results demonstrate that decreased expression of ASPP1 in patients with ALL is due to anabnormal methylation of its promoter and is associated with a poor prognosis.