Detection of TP53 dysfunction in chronic lymphocytic leukemia by an in vitro functional assay based on TP53 activation by the non-genotoxic drug Nutlin-3: a proposal for clinical application.

ABSTRACT:

Background

TP53 defects, i.e., 17p13 deletion and/or nucleotide mutations, associate with short survival and chemorefractoriness in chronic lymphocytic leukemia (CLL). In this context, since direct sequencing of the TP53 gene does not evaluate TP53 functionality, a functional assessment of TP53 pathway may be of interest to identify high risk CLL. By taking advantage of a training cohort of 100 CLL and a validation cohort of 40 CLL with different patterns of TP53 mutation/deletion by FISH and sequencing, we propose an in-vitro assay in which the modulation of TP53 protein and CDKN1A mRNA were investigated upon 24-hour exposure of CLL cells to Nutlin-3.

Methods

The functional assay was set-up on cell lines recapitulating all TP53 genotypes (EHEB, TP53(wt/wt); RAJI, TP53(mut/w

SUBMITTER: Pozzo F 

PROVIDER: S-EPMC4222122 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature