Alternative pre-mRNA splicing leads to potential biomarkers in diffuse large B-cell lymphoma - a systematic review

INTRODUCTION: The study of potential biomarkers in haema-tological malignancies has gained momentum in past decades. We compiled a systematic review to outline potential biomarkers based on alternative pre-mRNA splicing that were suggested to be clinically useful for the diagnosis, prognosis and response to therapeutics in diffuse large B-cell lymphoma (DLBCL). METHODS: A comprehensive search of the literature in PubMed, Embase and Scopus was performed and supplemented with screening of reference lists. Only articles concerning potential biomarkers originating from reports on alternative pre-mRNA splicing were included. The contributions of these studies will help develop personalised medicine. Therefore, the clinical utility of the potential biomarkers was evaluated. RESULTS: A total of 16 studies were included of which eight described seven different potential diagnostic biomarkers. Eight studies reported two potential prognostic biomarkers for CD44, its spliced mRNA variants and the resulting proteins that were the most frequently reported. Furthermore, two studies reported two proteins originating from alternative pre-mRNA splicing as potentially predictive biomarkers. CONCLUSIONS: Alternative pre-mRNA splicing is a promising potential diagnostic, prognostic and predictive biomarker for the identification of pathogenic impacts in DLBCL. The use of these potential biomarkers in the clinical management of DLBCL awaits prospective clinical validation supporting its potential to contribute to the shift towards more personalised medicine.