Clinical Significance of microRNAs in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation

Abstract

Hematologic 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.

The Role of MicroRNA in Graft-Versus-Host-Disease: A Review

“… Schematic representative mechanism of action of the miRNAs studied in this review. Inspired by Sevcikova’s group [ 61 ]. The works studied in this review have highlighted that the miRNAs involved in aGVHD (green box) and cGVHD (red box) could be the biomarkers involving the NF-kB, INF- α/γ, and TNF-α pathways, which increase the levels of oxidative stress and cause apoptosis of cells in the target organs of aGVHD, and some of cGVHD.…”

MicroRNAs as Potential Graft Rejection or Tolerance Biomarkers and Their Dilemma in Clinical Routines Behaving like Devilish, Angelic, or Frightening Elements

“…On the other hand, these molecules could also have an essential function in cold ischemia-reperfusion injury, as previously reported [67,68]. Additionally, since their discovery, research on miRNA expression profiles has shown promise for predicting kidney graft status in a variety of clinical contexts, including acute or delayed graft function, rejection, liver and heart transplant, hematological transplantation, or bone fragility in chronic kidney disease [6,26,[69][70][71][72][73][74][75].…”

“…A three-microRNA acute rejection signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients suffering acute rejection. Other authors also provide a summary of information about the therapeutic relevance of aberrant miRNA expression profiles in hematologic cancer patients and their relationships with various antagomiRs, mimetics, and circular RNAs (circRNAs), as well as with diagnosis, prognosis, and therapy response monitoring [70]. A narrative review written by a different group also examined whether miRNAs could aid in treating osteoporosis and renal osteodystrophy [26].…”

Serum Levels of miR-122-5p and miR-125a-5p Predict Hepatotoxicity Occurrence in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

“…The focus on serum miRNAs stems from the clinical availability, reliability, and ease of introducing blood-based biomarker tests to clinical practice. Serum miRNAs, released into circulation by various cell types, including hematopoietic and non-hematopoietic cells, would thus provide a more comprehensive insight into the incipient complications and outcome predictions [49][50][51]. In addition, assessment of miR-122 in other populations, including allogeneic hematopoietic stem cell transplant recipients, would be exciting in the context of hepatic GvHD, as miR-122 was already reported to be up-regulated in sera of patients with chronic GvHD [52].…”