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A plasma microRNA signature as a biomarker for acquired aplastic anemia

Journal Title: 
Primary Author: 
Hosokawa K, Kajigaya S, Feng X, Desierto MJ, Fernandez Ibanez MD, Rios O, Weinstein B, Scheinberg P, Townsley DM, Young NS
Original Publication Date: 
Thursday, September 22, 2016

Aplastic anemia is an acquired bone marrow disease characterized by marrow hypoplasia, a paucity of hematopoietic stem and progenitor cells, and pancytopenia of the peripheral blood, due to immune attack on the bone marrow. In aplastic anemia, a major challenge is to develop immune biomarkers to monitor the disease. We analyzed circulating miRNAs in plasma samples of aplastic anemia patients in order to identify disease-specific miRNAs. A total of 179 miRNAs were analyzed in 35 plasma samples from 13 aplastic anemia, 11 myelodysplastic syndrome, and 11 healthy controls using the Serum/Plasma Focus microRNA PCR Panel. Subsequently, 19 miRNAs from the discovery set were investigated in the 108 plasma samples from 41 aplastic anemia, 24 myelodysplastic syndrome, and 43 healthy controls for validation, confirming that three miRNAs could be validated as dysregulated (> 1.5 fold change) in aplastic anemia, compared to healthy controls. MiR-150-5p (induction of T-cell differentiation) and miR-146b-5p (involvement in the feedback regulation of innate immune response) were elevated in aplastic anemia plasma, whereas miR-1 was decreased in aplastic anemia. By receiver-operating characteristic curve analysis, we developed a logistic model with these three miRNAs that enabled us to predict the probability of a diagnosis of aplastic anemia with an area under the curve of 0.86. Dysregulated expression levels of the miRNAs were normalized after immunosuppressive therapy at 6 months. Specifically, miR-150-5p expression was significantly reduced after successful immunosuppressive therapy, but did not change in non-responders. We propose three novel plasma biomarkers in AA, in which miR-150-5p, miR-146b-5p, and miR-1 can serve for diagnosis and miR-150-5p for disease monitoring.

Bone Marrow Disease(s): 
  • aplastic anemia
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