Circulating microRNAs (miRNAs) are potential biomarkers for cancer. We examined plasma levels of 2 miRNAs, let-7a and miR-16, in 50 patients with myelodysplastic syndrome (MDS) and 76 healthy persons using quantitative real-time PCR. Circulating levels of both miRNAs were similar among healthy controls but were significantly lower in MDS patients (P ؍ .001 and P < .001, respectively). The distributions of these 2 miRNA levels were bimodal in MDS patients, and these levels were significantly associated with their progression-free survival and overall survival (both P < .001 for let-7a; P < .001 and P ؍ .001 for miR-16). This association persisted even after patients were stratified according to the International Prognostic Scoring System. Multivariate analysis revealed that let-7a level was a strong independent predictor for overall survival in this patient cohort. These findings suggest that let-7a and miR-16 plasma levels can serve as noninvasive prognostic markers in MDS patients. (Blood. 2011;118(2):413-415)
IntroductionMyelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by abnormalities of bone marrow hematopoietic cells and the microenvironment. MDS patients have a variable risk of transformation to acute myeloid leukemia, and transformation is believed to be a multistep process that requires the accumulation of genetic and epigenetic alterations. 1,2 Alterations in apoptosis and proliferation have been implicated in the pathogenesis of MDS, but the mechanisms underlying these alterations are incompletely understood. The widely used risk model, the International Prognostic Scoring System (IPSS), integrates cytogenetics, morphology, and clinical features but is limited in its ability to predict MDS patient outcomes. 3-5 Molecular markers are needed to improve prediction accuracy. 6 MicroRNAs (miRNAs) are a recently discovered class of short (19-25 nt), naturally occurring, single-stranded RNA molecules that are components of the epigenetic machinery. 7 MiRNAs regulate the expression of target genes posttranscriptionally, mostly by inhibiting translation or inducing mRNA degradation. MiRNAs also play important roles in the regulation of DNA methylation and histone modification and can function as oncogenes, tumor suppressor genes, or both. MiRNAs have been specifically implicated in the development of solid and hematopoietic malignancies. 8 Recently, miRNAs were identified in several types of body fluid, from both healthy individuals and patients with various types of cancer, and may therefore have potential as noninvasive biomarkers of cancer. 9-13 One recent study found that plasma levels of miR-92 may be a biomarker for acute myeloid leukemia. 14 Two miRNAs, let-7a and miR-16, are known to play important roles in myeloid leukemogenesis by regulating the cell cycle and apoptosis, 15-18 both of which are important in MDS pathogenesis. We decided to focus on these 2 miRNAs that are known to be down-regulated in leukemias. The goal of the present study was to analyze...
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