Alteration of p73 in pediatric de novo acute lymphoblastic leukemia.

Abstract:

:The frequency of p73 mutation is low in hematologic malignancies as well as solid tumors. Aberrant DNA methylation of multiple promoter associated CpG islands is a frequent phenomenon in acute lymphoblastic leukemia (ALL). In the present study, we scanned for mutations in the exons 4, 5, 6, and 7 of p73 gene. Using PCR-based methylation analysis, we have explored the prevalence of methylation of this pathway in a cohort of children with ALL (N=120). One pediatric patient showed mutation in exon 4, two showed mutation in exon 5, and none of the patients showed mutation in exons 6 and 7. Methylation of p73 gene is absent in the patients studied. Expression level of p73 m RNA was also examined in 40 ALL samples using reverse transcriptase/polymerase chain reaction. All the patients showed p73 mRNA expression. However, p73 overexpression was observed in 58% of pediatric patients as demonstrated by immunocytochemistry and Western blot analysis. Further, mutation of p73 has been correlated with p73 m RNA and p73 protein status. The results show the presence of overexpressed protein in the samples with mutated p73 gene. Thus, it is presumed that mutation of p73 might lead to production of defective p73 protein and this might have a role in the process of leukemogenesis of ALL. Methylation of p73 does not play a role in pediatric ALL patients of our population. This report is the first demonstrating the presence of p73 gene mutations in exons 4 and 5 with overexpression of p73 protein and absence of p73 methylation in pediatric ALL patients of eastern Indian population.

authors

Sahu GR,Das BR

doi

10.1016/j.bbrc.2004.12.064

subject

Has Abstract

pub_date

2005-02-18 00:00:00

pages

750-5

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(04)02865-7

journal_volume

327

pub_type

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