MicroRNA Fingerprints in Patients with Myelodysplastic Syndrome Identify miR-Let7a and miR-16 as Potential Diagnostic Markers
HM de Paula, G Calin, LJ Medeiros, M Fernandez, G Garcia-Manero, CE Bueso-Ramos. University of Sao Paulo School of Medicine, Sao Paulo, SP, Brazil; MD Anderson Cancer Center, Houston, TX
Background: The pathophysiology of myelodysplastic syndromes (MDS) is poorly understood, and despite recent advances in the management MDS patients still have a poor outcome. Alterations in apoptosis and proliferation are involved in the pathogenesis of MDS. MicroRNAs are a newly discovered class of short (19-25 nt), naturally occurring, single-stranded RNA molecules that regulate the expression of target genes, either by repressing translation or inducing mRNA degradation. miR-Let7a and miR-16 are known to be important regulators of the cell cycle and apoptosis. We hypothesized that miR-Let7a and miR-16 expression levels in plasma may be altered in MDS patients.
Design: We analyzed miR-16 and Let7a levels by quantitative real time PCR in plasma samples of patients with MDS and normal controls. 56 MDS patients formed the study group: 22 refractory anemia with multilineage dysplasia (RCMD), 9 refractory anemia with multilineage dysplasia and ringed sideroblasts (RCMD-RS), 9 refractory anemia with excess blasts – 1 (RAEB-1), 11 RAEB-2, 2 therapy-related MDS (t-MDS), 1 MDS associated with isolated del(5q), and 2 refractory anemia with ringed sideroblasts (RARS). The control group included plasma samples from 76 normal donors.
Results: miR-Let7a and miR-16 were significantly down-regulated in MDS patients compared with the control group (p=0.008 and p=0.04, respectively). Expression levels of miR-16 were significantly more down-regulated in high grade (RAEB) than in lower grade MDS (RCMD) cases (p = 0.02).
Conclusions: We propose that miR-Let7a and miR-16 plasma levels correlate with the clinical aggressiveness of MDS, and potentially can be used as early markers of MDS.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 163, Tuesday Afternoon