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

被引:2
作者
Braga, Tatiane Vieira [1 ]
Gontijo Evangelista, Fernanda Cristina [1 ]
Santiago, Marie Gabriele [1 ]
Menezes Ferrao, Aline Lucia [1 ]
de Almeida, Tamara Dauare [1 ]
da Fonseca Barbosa, Barbara Lima [1 ]
da Silva Araujo, Sergio Schusterschitz [2 ]
Ribeiro, Glaciano Nogueira [2 ]
Carvalho, Maria das Gracas [1 ]
Sabino, Adriano de Paula [1 ]
机构
[1] Univ Fed Minas Gerais, Clin & Toxicol Anal Dept, Sch Pharm, Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Clin Hosp, Belo Horizonte, MG, Brazil
关键词
CLL; miR-15a; miR-16-1; Biomarkers; DOWN-REGULATION; MESSENGER-RNA; EXPRESSION; SURVIVAL; APOPTOSIS; DELETION; GENES; CELLS; 13Q14; TIME;
D O I
10.1590/s2175-97902022e19332
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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-161, 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 (R-2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R-2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R-2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R-2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes ( R-2 = - 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.
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