Affiliations: [a] Institute of Hematology and Blood Transfusion, Prague, Czech Republic | [b] General University Hospital, Prague, Czech Republic
Correspondence:
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Corresponding author: Michaela Dostalova Merkerova, Institute of Hematology and Blood Transfusion, Prague, Czech Republic. E-mail: [email protected].
Abstract: BACKGROUND: Azacitidine (AZA) is a nucleoside analog used for treatment of myelodysplasia and the prediction of AZA responsiveness is important for the therapy management. METHODS: Using microarrays and reverse-transcription quantitative-PCR, we analyzed microRNA (miRNA) expression in bone marrow CD34+ cells of 27 patients with higher-risk myelodysplastic syndromes or acute myeloid leukemia with myelodysplasia-related changes before and during AZA treatment. RESULTS: At baseline, we found that future overall response rate was significantly higher in patients with upregulated miR-17-3p and downregulated miR-100-5p and miR-133b. Importantly, the high level of miR-100-5p at baseline was associated with shorter overall survival (HR = 4.066, P= 0.008). After AZA treatment, we observed deregulation of 30 miRNAs in responders (including downregulation of miR-10b-5p, miR-15a-5p/b-5p, miR-24-3p, and miR-148b-3p), while their levels remained unchanged in non-responders. CONCLUSIONS: Our study demonstrates that responders and non-responders have distinct miRNA patterns and that the level of specific miRNAs before therapy may predict the efficacy of AZA treatment.
