Written in Blood: Kissing Disease miRNAs Could Predict Outcome of Patients With Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukaemia (CLL) is themost common adult leuvariability in the choice of starting material (i.e. exosomes, sera or plaskaemia in the Western world and is characterized by the accumulation of CD5+/CD19+/CD23+ mature B cells in the peripheral blood, bone marrow and lymphoid tissue of patients. Despite major improvements in therapy over the past decades, CLL remains essentially an incurable disease. The clinical course of CLL is highly variable with life expectancies running from months to decades. The presence of recurrent chromosomal aberrations along with the mutation status of IGHV genes in the tumour cells of CLL patients are the current gold standards of clinical prognostication. However, these tests are laborious to implement and require techniques not readily available in all diagnostic laboratories. In this issue of EBioMedicine, Ferrajoli and colleagues propose that plasma and tumour cell-derivedmicroRNAs (miRNAs) encoded by Esptein– Barr virus (EBV), the causative agent of infectious mononucleosis (also known as kissing disease), could be useful diagnostic and prognostic biomarkers for this disease (Ferrajoli et al., 2015). Plasma biomarkers are an appealing prospect for clinical practice as the ability to directly measure molecules in the blood of CLL patients (or other types of cancer) without needing to purify tumour cells would almost certainly lead lower costs and shorten turnaround times for patients. The presence of nucleic acids (DNA) in the blood was first demonstrated over 60 years ago (Mandel andMetais, 1948), although their potential as a non-invasive biomarker of cancer was not recognised until some years later. It was however the 2008 discovery of microRNAs (miRNAs) in the blood of cancer patients (Lawrie et al., 2008; Mitchell et al., 2008) that has put the field in the spotlight and there are now more than 4500 publications on the subject (http://www.ncbi.nlm. nih.gov/pubmed). MiRNAs are particularly attractive candidates as non-invasive biomarkers as they are able to sub-classify cancers to a greater degree of accuracy than traditional gene expression analysis (Lu et al., 2005), and are protected from the high levels of RNase activity present in blood (Mitchell et al., 2008). Furthermore, unlike protein biomarkers which can persist in the blood for many weeks, the short halflife of circulating RNA makes it eminently suitable as a tool to monitor the evolution of a cancer in real-time allowing treatment decisions to be taken much more efficiently. Despite its promise, the study of circulating miRNA is very much in its infancy reflected in the many nonoverlapping and even contradictory studies have been published. On many occasions this disparity is due to technical factors particularly