An increased fraction of circulating miR-363 and miR-16 is particle bound in patients with chronic lymphocytic leukaemia as compared to normal subjects.

• Published in: BMC Research Notes
• Main Authors: Alharthi, Afaf, Beck, Daniel, Howard, Dena R., Hillmen, Peter, Oates, Melanie, Pettitt, Andrew, Wagner, Simon D.
• Format: Article in Journal/Newspaper
• Language: English
• Published: BioMed Central 2018
• Subjects: Chronic lymphocytic leukaemia; Extracellular vesicle; miRNA; Arctic; Leicester
• Online Access: https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-018-3391-9; http://hdl.handle.net/2381/42178; https://doi.org/10.1186/s13104-018-3391-9

The data that support the findings from the ARCTIC clinical trial (Reference 19) are available from the Leeds Clinical Trials Unit but restrictions apply to the availability of these data, which were used following completion of a Data Sharing Agreement between the universities of Leeds and Leicester and so are not publicly available. All other data generated or analysed during this study are included in this published article. OBJECTIVES: In vitro culture studies have shown that miR-363 is enriched in extracellular vesicles from chronic lymphocytic leukaemia cells. We wondered whether miR-363 was detectable in plasma, which is an essential precondition for further studies to assess its usefulness as a biomarker. Using samples from two clinical trials: one enrolling patients with advanced disease and the other asymptomatic patients with early stage disease, we determined plasma miR-363 levels and secondly investigated the distribution of this miRNA between plasma and particle bound fractions in patients and normal subjects. RESULTS: Advanced disease (n = 95) was associated with higher levels of miR-363 than early stage disease (n = 45) or normal subjects (n = 11) but there was no association with markers of prognosis. The distribution of specific miRNA between particle bound and plasma protein fractions was investigated using size exclusion chromatography on plasma from patients (n = 4) and normal subjects (n = 3). ~ 20% of total miR-16 and miR-363 is particle bound in patients while there was no detectable particle bound material in normal subjects. Our work demonstrates that miR-363 levels are raised in chronic lymphocytic leukaemia patients and raises the possibility that distribution of circulating miRNA between plasma fractions differs in health and disease. PhD studentship from the government of Saudi Arabia to AA. The UK CLL Trials Biobank, University of Liverpool is funded by Bloodwise. ARCTIC clinical trial funded by the NIHR Health Technology Assessment Programme (NIHR HTA Project Number 07/01/38; ISRCTN16544962). Peer-reviewed Publisher Version