Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia

• Published in: Brazilian Journal of Pharmaceutical Sciences Vol. 58
• Main Authors: Braga, Tatiane Vieira, Evangelista, Fernanda Cristina Gontijo, Santiago, Marie Gabriele, Ferrão, Aline Lúcia Menezes, Almeida, Tamara Dauare de, Barbosa, Bárbara Lima da Fonseca, Araujo, Sergio Schusterschitz da Silva, Ribeiro, Glaciano Nogueira, Carvalho, Maria das Graças, Sabino, Adriano de Paula
• Format: Journal Article
• Language: English
• Published: Universidade de São Paulo, Faculdade de Ciências Farmacêuticas 2022; Universidade de São Paulo
• Subjects: Biomarkers; CLL; miR-15a; miR-16-1; PHARMACOLOGY & PHARMACY; Biomarkers; CLL; miR-15a; miR-16-1
• ISSN: 2175-9790; 2175-9790
• DOI: 10.1590/s2175-97902022e19332

Abstract Chronic lymphocytic leukemia (CLL) is a blood cancer characterized by the accumulation of clonal B-lymphocytes. This study evaluated the mRNA gene expression of miR-15a, miR-16- 1, ZAP-70, and Ang-2 by qPCR, as well as the plasma levels of Bcl-2 by Elisa immunoassay, in CLL patients and healthy controls. Significant differences were observed when comparing patients and controls regarding miR-15a (p < 0.001), miR-16-1 (p < 0.001) mRNA, Ang-2 gene expression, and Bcl-2 plasma levels (p < 0.001). When stratified by risk, differences were maintained with a significantly reduced expression in high-risk patients. A positive correlation was observed between miR-15a and platelets (R2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes (R2 = - 0.515; p = 0.00004). The data suggest that a reduction in miR-15a and miR-16-1 expressions, in addition to an overexpression of Bcl-2, are associated with the reduction in apoptosis and, consequently, to a longer survival of lymphocytes, thus contributing to lymphocyte accumulation and aggravation of the disease. By contrast, Ang-2 expression was significantly higher in A than in B + C Binet groups. This context leads to the speculation that this biomarker should be investigated in more robust studies within populations with a still relevantly indolent form of the disease in an attempt to identify those patients with a greater potential for an aggravation of the disease.