MicroRNA 16-1 Predicts Time-to-Treatment (TTT) in Chronic Lymphocytic Leukemia
Prabhjot Kaur, Heather B Steinmetz, Claudine L Lefferts, Alexey V Danilov, Gregory J Tsongalis. Dartmouth-Hitchcock Medical Center, Lebanon, NH
Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world and is a very clinically heterogeneous disease for which better prognostic biomarkers are needed. microRNAs (miRNAs) are small endogenous, non-coding 22-nucleotide regulatory RNAs that have been shown to modulate hematopoietic lineage differentiation and play important gene-regulatory roles in disease processes. In this study, we evaluated the expression of miR16-1 and correlated its expression with prognostic factors in patients with CLL.
Design: In this study, miRNA was isolated from B-cell enriched peripheral blood from 60 CLL samples that was passed thru a ficoll hypaque gradient. Total RNA was extracted using the mirVana™ miRNA Isolation Kit (Ambion). Expression of miR16-1 and U47 (an endogenous control) was determined using the ΔΔCTmethod (ΔCTCLL sample - ΔCTnormal). All values were normalized to the U47 control miRNA and a significant result was considered as a change greater than 1 log. Log rank and Chi-square tests were used to analyze the data.
Results: 60 patients with CLL entered the study, 33 males, 27 females. Median age -67 years. Median follow-up of 60 months. Compared with normal donor B-cells, miR 16-1 transcript levels were low in 33 CLL samples (55%). Using a cutoff of >50% reduction in miR16-1 transcript level compared to normal B-cells, CLL samples were divided in two subsets: low and normal/high. Patients with low miR16-1 levels had low stage disease at presentation (Rai stage 0-1, P=0.012). At 5 years of follow-up, median TTT was 94.7 months in patients with low miR16-1 vs. 65.9 months in patients who exhibited normal/high expression (hazard ratio 3.20, 95% CI 1.07 to 6.50, p=0.035.)
Conclusions: Here we demonstrate that lower levels of mir-16-1 transcripts are seen in patients with CLL who present in Rai stages 0-1. Low miR16-1 expression also predicts longer time-to-treatment(TTT). Thus, miR16-1 may serve as a prognostic marker in CLL.
Monday, March 19, 2012 1:00 PM
Poster Session II # 201, Monday Afternoon