Loss of MIR15A and MIR16‐1 at 13q14 is associated with increased TP53 mRNA, de‐repression of BCL2 and adverse outcome in chronic lymphocytic leukaemia. (18th July 2014)

• Record Type: Journal Article
• Authors: Lin, Ke; Farahani, Mosavar; Yang, Yi; Johnson, Gillian G.; Oates, Melanie; Atherton, Mark; Douglas, Angela; Kalakonda, Nagesh; Pettitt, Andrew R.
• Is Part Of: British journal of haematology. Volume 167:Number 3(2014:Nov.)
• Page Start: 346
• Page End: 355
• Publication Date: 2014-07-18
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13043
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh13043-abs-0001"> <title>Summary</title> <p>This study was conducted to investigate the possibility that <italic>TP53 </italic>mRNA is variably expressed in chronic lymphocytic leukaemia (CLL) and that under‐expression is associated with TP53 dysfunction and adverse outcome. Although <italic>TP53 </italic>mRNA levels did indeed vary among the 104 CLL samples examined, this variability resulted primarily from over‐expression of <italic>TP53 </italic>mRNA in 18 samples, all of which lacked <italic>TP53</italic> deletion/mutation. These patients had higher lymphocyte counts and shorter overall and treatment‐free survival times compared to cases with low <italic>TP53 </italic>mRNA expression and no <italic>TP53</italic> deletion/mutation. Furthermore, <italic>TP53 </italic>mRNA levels did not correlate with levels of TP53 protein or its transcriptional target CDKN1A. We speculated that the adverse outcome associated with <italic>TP53 </italic>mRNA over‐expression might reflect variation in levels of <italic>MIR15A</italic> and <italic>MIR16‐1, </italic> which are encoded on chromosome 13q14 and target <italic>TP53</italic> and some oncogenes including <italic>BCL2</italic>. In keeping with our hypothesis, 13q14 copy number and levels of <italic>MIR15A/MIR16‐1</italic> correlated positively with one another but negatively with levels of <italic>TP53 </italic>mRNA and <italic>BCL2 </italic>mRNA. Our findings support a model in which loss of <italic>MIR15A/MIR16‐1</italic> at chromosome 13q14 results in adverse outcome due to de‐repression of oncogenes such as <italic>BCL2</italic>, and up‐regulation of <italic>TP53 </italic>mRNA as a bystander effect.</p> </abstract>