Recently, extracellular circulating microRNAs were also detected in body fluids, such as serum, plasma, saliva and urine (7). These circulating microRNAs are believed to be chaperoned by various carriers, such as secreted mem- MicroRNAs (or miRs) play a crucial role in chronic lymphocytic leukemia (CLL) physiopathology and prognosis. In addition, circulating microRNAs in body fluids have been proposed as new biomarkers. We investigated the expression of matched cellular and serum circulating microRNA-150 by quantitative real-time PCR (qPCR) from purified CD19 + cells or from CLL serums obtained at diagnosis in a cohort of 273/252 CLL patients with a median follow-up of 78 months (range 7-380) and correlated it to other biological or clinical parameters. We showed that miR-150 was significantly overexpressed in CLL cells/serums compared with healthy subjects (P < 0.0001). Among CLL patients, a low cellular miR-150 expression level was associated with tumor burden, disease aggressiveness and poor prognostic factors. In contrast, a high level of serum miR-150 was associated with tumor burden markers and some markers of poor prognosis. Similarly, cellular and serum miR-150 also predicted treatment-free survival (TFS) and overall survival (OS) in an opposite manner: patients with low cellular/serum miR-150 levels have median TFS of 40/111 months compared with high-level patients who have a median TFS of 122/60 months (P < 0.0001/P = 0.0066). Similar results were observed for OS. We also found that cellular and serum miR-150 levels vary in an opposite manner during disease progression and that cellular miR-150 could be regulated by its release into the extracellular space. Cellular and serum levels of miR-150 are associated with opposite clinical prognoses and could be used to molecularly monitor disease evolution as a new prognostic factor in CLL. brane vesicles (exosomes from 50 to 100 nm and microvesicles from 100 nm to 1 μm) or protein/lipid complexes (8,9), since carrier-free microRNAs will be degraded by RNase digestion and other environmental factors (9). Their levels and composition have been shown to be modulated with injury conditions as well as tumor burden (10-12). For these reasons, extracellular microRNAs could be used as informative biomarkers to assess and monitor disease evolution (11,13). Moussay et al. (14) recently observed that some circulating microRNAs in CLL plasma could be used as prognostic factors. Among these, microRNA-150 warranted further investigation for a number of reasons. This microRNA plays an important role in normal and malignant hematopoiesis (15). In addition, plasma (14) and cellular (16,17) microRNA-150 were both downregulated in poor prognosis CLL patients based on ZAP70 and IgHV mutational status. A low level of cellular microRNA-150 was also observed in CLL proliferation centers (18), and microRNA-150 is differentially expressed according to the stereotyped B-cell receptor (BCR) subset taken into consideration (19), emphasizing its pivotal role in CLL. Finally, a recent s...