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MICRORNA 99B and LET7A as diagnostic parameters in myelodysplastic syndrome

Background: Myelodysplastic syndrome (MDS) is heterogenous disorder with variable outcomes. Although there are well known and clinically useful prognostic scoring systems, the natural history of MDS is unpredictable. Recent years have shown several noninvasive diagnostic models in MDS. As there are significant epigenetic mechanisms in MDS pathogenesis, microRNA can serve as suitable diagnostic parameters in MDS. Aims: We have investigated weather the miRNA expression profiling (miR-125a, miR-99b, miR-125b and let-7a) could serve as an additional diagnostic method for the early and noninvasive diagnosis of MDS. Methods: Whole blood from 26 healthy volunteers and 44 MDS diagnosed patients (70% male, 30% female, median age 68) was drawn into EDTA containing tubes (BD Vacutainer) in our national MDS Reference Center. 88% of MDS patients were in International Prognostic Scoring System (IPSS) lower group, while 12% were in higher risk group. The blood was processed to plasma separation, miRNAs extraction (miRNeasy Serum/Plasma Kit, by QIAGEN GMBH)) and reverse transcription (miScript II RT Kit, by QIAGEN GMBH). miRNA expression profiling (miScript SYBR Green PCR Kit/Custom PCR Array) was performed on TaqMan qPCR platform in molecular laboratory accredited according ISO 15189. Data normalization (miR-126-3p) and data analysis (webbased software) were done according to the manufacturer instructions (Qiagen). Results: Results. Statistically significant differences of miRNAs fold changes between healthy volunteers and MDS diagnosed patients were observed for let-7a (P = 0, 030) and miR-125a (P = 0, 021). Both miRNAs were down-regulated in MDS diagnosed patients (-7.34 vs. -1.03), but only let- 7a expressed over 2-fold change of healthy volunteers. miR-99b and miR- 125b were up- regulated (4.46 vs. 1.88) in MDS diagnosed patients, but only miR-99b expressed over 2-fold change of healthy volunteers. Summary/Conclusion: Conclusions. Several miRNAs were found to be associated with diagnosis in MDS. Significant down-regulation of let-7a as well as up-regulation of miR-99b in MDS patients could serve as a new noninvasive diagnostic molecular biomarkers in MDS diagnosis. Further investigations are needed to define the mechanism of miRNA in MDS pathogenesis and prognosis.

myelodysplastic syndrome ; MICRORNA 99B ; LET7A

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