Small molecules of great importance

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The cure rates for ALL are remarkably high (90%). This has been achieved due to chemotherapy protocols based on high doses of drugs. Unfortunately, this is associated with adverse effects of therapy in almost 75% of patients. Therefore, biomarkers that could indicate a higher risk of adverse effects are being searched for so that they can be prevented. miRNAs have recently been explored as such potential markers.

Material and Methods: A systematic review of scientific articles available in the PubMed, WOS, Medline and Google Scholar databases was conducted using the following keywords: “miRNA”, “chemotherapy toxicity”, “acute lymphoblastic leukemia”. Only full-text articles from 2014-2024 about children were included. We analyzed 21 studies.

Results: miRNAs are a good potential diagnostic, prognostic and predictive marker in ALL. Moreover, overexpression of miR-29b (AUC=0.75) and miR-499 (AUC=0.82) is useful in identifying patients at high risk of cardiomyopathy after anthracycline treatment and as an early marker of myocardial damage. Furthermore, some miRNAs have been associated with hepatotoxicity (miR-1208; OR=1.15), oral mucositis (miR-4268, OR=1.31; miR-1206; OR=3.6), hematotoxicity (miR-1206, OR=2.3; miR-323b, OR=0.36) and gastrotoxicity (miR-323b, OR=0.23; miR-4751, OR=12.38; miR-3117, OR=0.24) caused by methotrexate administration. Reduced expression of miR-24 (OR=0.43) also correlates with the toxicity of this drug at higher doses. In addition, changes in the expression and/or specific single-nucleotide polymorphisms of the target genes of miR-202 (OR=2.88), miR-4481 (OR=2.56), miR-3117, (OR=0.18) and miR-6067 (OR=0.58) correlate with vincristine neurotoxicity. Moreover, overexpression of miR-155 (rho=0.7) and reduced expression of miR-146a (rho=-0.67) are associated with gastrotoxicity after myeloablative conditioning before allogeneic hematopoietic stem cell transplantation.

Conclusions: The determination of changes in expression levels and/or single-nucleotide polymorphisms of target genes for specific miRNAs is a good potential tool for identifying patients at risk of developing complications during chemotherapy.