Simple SummaryDysregulated microRNA (miRNA) expression has been described in the initiation and progression of a wide spectrum of hematologic malignancies. Moreover, aberrant miRNA expression patterns have been shown to be involved in severe post-transplant complications in patients receiving hematopoietic stem cell transplantations (HSCT), suggesting their use as promising diagnostic and prognostic biomarkers for acute graft-versus-host disease (aGvHD). Recently, activation or inhibition of deregulated miRNAs appears to be an attractive therapeutic option for increasing treatment efficacy. Further research concerning the associations between alterations in miRNA levels and malignant hematopoiesis and treatment response might bring new possibilities for specific miRNA-based approaches to improve the outcomes for hematologic cancer patients.AbstractHematologic malignancies are a group of neoplastic conditions that can develop from any stage of the hematopoiesis cascade. Small non-coding microRNAs (miRNAs) play a crucial role in the post-transcriptional regulation of gene expression. Mounting evidence highlights the role of miRNAs in malignant hematopoiesis via the regulation of oncogenes and tumor suppressors involved in proliferation, differentiation, and cell death. In this review, we provide current knowledge about dysregulated miRNA expression in the pathogenesis of hematological malignancies. We summarize data about the clinical utility of aberrant miRNA expression profiles in hematologic cancer patients and their associations with diagnosis, prognosis, and the monitoring of treatment response. Moreover, we will discuss the emerging role of miRNAs in hematopoietic stem cell transplantation (HSCT), and severe post-HSCT complications, such as graft-versus-host disease (GvHD). The therapeutical potential of the miRNA-based approach in hemato-oncology will be outlined, including studies with specific antagomiRs, mimetics, and circular RNAs (circRNAs). Since hematologic malignancies represent a full spectrum of disorders with different treatment paradigms and prognoses, the potential use of miRNAs as novel diagnostic and prognostic biomarkers might lead to improvements, resulting in a more accurate diagnosis and better patient outcomes.