Circulating exosomal microRNAs in acquired aplastic anemia and myelodysplastic syndromes
EHA Learning Center. Giudice V. Jul 1, 2018; 224107
Topic: 1B Bone marrow failure
Valentina Giudice
Valentina Giudice
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Co-Authors: Lauren G. Banaszak, Fernanda Gutierrez-Rodrigues, Sachiko Kajigaya, Reema Panjwani, Maria del Pilar Fernandez Ibanez, Olga Rios, Christopher K. Bleck, Erin S. Stempinski, Diego Quinones Raffo, Danielle M. Townsley, Neal S. Young

Abstract: Exosomal microRNAs modulate cancer cell metabolism and the immune response. Specific exosomal microRNAs have been reported to be reliable biomarkers of several solid and hematologic malignancies. We examined the possible diagnostic and prognostic values of exosomal microRNAs in two human bone marrow failure diseases: aplastic anemia and myelodysplastic syndromes. After screening 372 microRNAs in a discovery set (n=42) of plasma exosome samples, we constructed a customized PCR plate, including 42 microRNAs, for validation in a larger cohort (n=99). We identified 25 differentially expressed exosomal microRNAs uniquely or frequently present in aplastic anemia and/or myelodysplastic syndromes. These microRNAs could be related to intracellular functions, such as metabolism, cell survival, and proliferation. Clinical parameters and progression-free survival were correlated to microRNA expression levels in aplastic anemia and myelodysplastic syndrome patients before and after six months of immunosuppressive therapy. One microRNA, mir-126-5p, was negatively correlated with a response to therapy in aplastic anemia: patients with higher relative expression of miR-126-5p at diagnosis had the shortest progression-free survival compared to those with lower or normal levels. Our findings suggest utility of exosomal microRNAs in the differential diagnosis of bone marrow failure syndromes. (Registered at clinicaltrials.gov identifiers: 00260689, 00604201, 00378534, 01623167, 00001620, 00001397, 00217594).

Article Number: 1150

Doi: 10.3324/haematol.2017.182824

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