MiR-181b is a biomarker of disease progression in chronic lymphocytic leukemia
A partir de l'analyse de séries d'échantillons prélevés sur 114 patients atteints d'une leucémie lymphocytaire chronique, cette étude montre que le micro-ARN 181b est un biomarqueur de la progression de la maladie
MicroRNAs play a crucial role in Chronic Lymphocytic Leukemia (CLL). We investigated whether microRNAs can discriminate patients with a progressive disease from those with a stable disease. We analyzed microRNA expression on leukemic cells isolated from 358 sequential samples of 114 patients with either stable or progressive disease. We find that during the course of the disease the expression values of miR-181b, the most dysregulated microRNA, decreased in samples of patients with a progressive (P<.001, training and validation sets) but not in those of patients with a stable disease (P=.3, training set; P=.2, validation set) over time. A drop of 50% or more between sequential samples and/or a miR-181b value ≤0.005 at the starting time point were significant to differentiate progressive from stable disease (P=.004, training set; P<.001, validation set). These parameters were associated with high risk of requiring treatment (risk ratio, 5.8; 95% confidence interval, 2.5-14.9). We also observed that miR-181b targets Mcl-1 protein and the decrease of its expression inversely correlated with increased protein levels of Mcl-1 and Bcl-2 target genes. We conclude that parameters defined on the basis of the miR-181b expression values specify disease progression in CLL and are associated with clinical outcome.
Blood , résumé, 2011