Publication Date:
2013-11-15
Description:
Background Disruptions of the TP53 tumor suppressor pathway by TP53 gene mutations and/or by17p deletions resulting in loss of the TP53 locus are clearly associated with poor survival and chromosomal instability in chronic lymphocytic leukemia (CLL). Chromosomal instability is promoted by telomere dysfunction, and the TP53 pathway is involved in the monitoring of telomere integrity. Aim The purpose of the present study was to describe the changes in main telomeric parameters, which can affect telomere integrity, associated with TP53 mutations and 17p deletions and to evaluate their potential prognostic value. Patients and Methods We performed a comparison between a group of TP53 disrupted CLL patients (n= 24) and a group of TP53 wild-type CLL patients (n= 61). Median age was 70 [39-89] years, M/F ratio was 2.4/1. At the time of sampling, 35 patients were in Binet stage A, 19 patients in stage B and 31 patients in stage C. A total of 50 patients were subsequently treated by immunochemotherapy (FCR n= 30, other n= 8), alemtuzumab (n= 8) or alkylating agent-based regimens (n= 4). TP53 gene mutation screening was performed using Sanger sequencing of the entire coding region (exons 2–11). Cytogenetic analysis (karyotype and FISH) were performed to evaluate the chromosomal instability and detect the marks of telomeric fragility. Quantitative PCR approaches were used to measure the relative telomere length and to evaluate expression levels of shelterin genes (TRF1, TRF2, POT1, RAP1, TPP1, and TIN2) and telomerase (hTERT). Results The patients showing a TP53 mutation without a 17p deletion and the patients carrying a 17p deletion with or without TP53 mutation appear to display the same level of telomeric instability. These cases are characterized by significant telomeric erosion (P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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