Avaliação dos níveis de expressão dos genes DDX41 e STING em pacientes portadores de Síndrome Mielodisplásica

Abstract

Myelodysplastic Syndrome (MDS) is an onco-hematological disease that affects the bone marrow and has a heterogeneous character. The main manifestations of the disease are the presence of cytopenias, dysplasia of one or more cell lines, ineffective hematopoiesis and risk of progression to acute myeloid leukemia. Aging is one of the main risk factors for the disease and because of that the incidence of MDS is higher in elderly people. The pathogenesis of MDS involves cytogenetic alterations and gene mutations in more than 80% of cases, and genes involved in DNA repair, DNA methylation and RNA splicing are often unregulated in MDS. Furthermore, overexpression of genes related to the immune system is observed in about 50% of patients, which results in a profile of chronic immune stimulation. The aim of this study was to evaluate changes in gene expression of two genes that play a role in the innate innate system: DDX41 and STING in patients with MDS. Bone marrow samples were collected from 73 individuals diagnosed with MDS at a tertiary hospital and 4 healthy controls. The cytogenetic study was performed by banda-G and to analyze the expression levels the real-time PCR methodology (RT-qPCR) was used. Gene expression levels were associated with cytogenetic alterations, clinical and laboratory variables of prognostic impact. We found that DDX41 had a higher expression level in patients with bone marrow blast counts greater than 10% compared to patients who had ≤ 2% blasts and between 5% - 10% blasts (p=0.002 and p=0.037, respectively) ; greater expression in patients with blasts > 5% compared to patients with blasts ≤ 5% (p=0.017); greater expression in patients with the SMD-EB2 subtype, a subtype that has a higher percentage of blasts in the medulla and has a more aggressive profile, compared to patients of the SMD-DM subtype, an intermediate subtype (p=0.004) and greater expression in patients with advanced forms of the disease when compared to patients with early forms of the disease (p=0.028). STING showed a similar behavior and we observed greater expression of this gene in patients with blast counts in bone marrow between 5% - 10% when compared to patients who had ≤ 2% blasts (p=0.016); greater expression in patients who had 3 cytopenias compared to those who had 1 cytopenia (p=0.006); greater expression in patients with the SMD-EB1 subtype, compared to patients with the SMD-SA subtype, a generally less aggressive subtype (p=0.013); greater expression in patients with more advanced forms of MDS, including (p=0.006) or not the MDS-DM subtype (0.015) and greater expression in patients grouped in the high + very high risk category compared to patients grouped in the risk category very low + low (p=0.006). Ourfindings demonstrate that DDX41 and STING may be involved in the pathogenesis and evolution of MDS.