title: A plasma microRNA signature as a biomarker for acquired aplastic anemia.
abstract: Aplastic anemia is an acquired bone marrow failure 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 measured circulating microRNAs in plasma samples of aplastic anemia patients in order to identify disease-specific microRNAs. A total of 179 microRNAs were analyzed in 35 plasma samples from 13 aplastic anemia patients, 11 myelodysplastic syndrome patients, and 11 healthy controls using the Serum/Plasma Focus microRNA Polymerase Chain Reaction Panel. Subsequently, 19 microRNAs from the discovery set were investigated in the 108 plasma samples from 41 aplastic anemia patients, 24 myelodysplastic syndrome patients, and 43 healthy controls for validation, confirming that 3 microRNAs 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 3 microRNAs 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 microRNAs became normal 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 3 novel plasma biomarkers in aplastic anemia, in which miR-150-5p, miR-146b-5p, and miR-1 can serve for diagnosis and miR-150-5p for disease monitoring. Clinicaltrials.gov identifiers:00260689, 00217594, 00961064.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MA, USA kohei.hosokawa@nih.gov.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hosokawa
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MA, USA.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kajigaya
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MA, USA.
authors.forename: Xingmin
authors.initials: X
authors.lastname: Feng
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MA, USA.
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Desierto
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MA, USA.
authors.forename: Maria Del Pilar
authors.initials: MD
authors.lastname: Fernandez Ibanez
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MA, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Rios
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Weinstein
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MA, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Scheinberg
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MA, USA.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Townsley
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MA, USA.
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000741:Anemia, Aplastic / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D015415:Biomarkers; D016022:Case-Control Studies; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000235:genetics; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D035683:MicroRNAs