Análise de Variantes Genéticas no gene da Endoglina em Leucemias Linfoblásticas Agudas de Células B Pediátricas

Abstract

Introduction: Endoglin (ENG, CD105) is a co-receptor part of the transforming growth factor beta (TGF-β) family, described as a powerful marker of the angiogenesis process. Recently, endoglin (ENG) has been increasingly studied in the context of hematopoietic neoplasms. ENG expression is reported in blasts in acute lymphoblastic leukemia (ALL) across different studies, and it is identified as a promising complementary diagnostic, prognostic, and therapeutic pathway. Therefore, this study examines the genetic variants rs11545664, rs35400405, and rs786514 in the ENG gene in pediatric B-cell acute lymphoblastic leukemia, as well as the measurement of soluble ENG (sENG). Material and Methods: The study involved 117 children aged 1 to 13 years in case (27) and control (90) groups. DNA was extracted and genetic variants were genotyped, RNA was extracted and converted for gene expression analysis, and sENG levels were measured. In silico analyses were also performed. Genotypic and allelic frequencies were then compared, along with sociodemographic data of cases and controls. The case group was stratified by genotypes for the selected genetic variants and analyzed according to clinical data, biochemical data levels, ENG gene expression, and sENG levels. Results: A significant difference was observed for rs7865146 in relation to platelet levels in the cases. Serum sENG levels in newly diagnosed pediatric B-ALL patients were higher compared to the control group (P <0.0001). No B-ALL patients died, and 23 (85.2%) patients were classified as low risk according to the NCI index. In silico analyses indicate the potential regulatory/functional involvement of the evaluated genetic variants. Conclusion: Our study did not present genetic data with significant or suggestive findings for B-ALL outcomes. Platelet levels were elevated for the TT genotype of the rs7865146 variant. This study reports elevated levels of circulating sENG at the time of diagnosis in pediatric B-ALL patients. Further studies are needed to expand knowledge about the role of ENG in the context of hematological neoplasms.