Diurnal proteomics and biomarker discovery in indolent versus aggressive chronic lymphocytic leukemia (CLL) patients: A proof of principle pilot study.

2014 
e22220 Background: In rodents, 10-20% of the genome has a 24-hour (h) rhythm in RNA expression. In a microarray study on RNA extracted from CLL cells sampled every 4 hours over 24 hours (6 samples) from 3 male and 6 female CLL patients (pts), we found gender differences in rhythmic RNA expression. We hypothesized that this might have clinical implication for biomarker discovery with some important biomarkers only found at certain times of day and with gender differences. Methods: Sampling for CLL cells and plasma was performed again at 6 time points in male (M) and female (F) CLL patients with indolent (10 pts, 5 M, 5 F) and aggressive CLL (10 pts, 5 M, 5 F). Each 8-plex iTRAQ block for mass spectrometry (MS) based relative quantification comprised all time points for a single patient and a universal control.More than 300 proteins were identified at a 95% confidence level in each iTRAQ experiment, with 74 showing differences in expression between aggressive and indolent pts and 44 proteins showing a signi...
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