Avaliação dos níveis de expressão dos genes alfa e beta Klotho em pacientes portadores de síndrome mielodisplásica.

Abstract

Myelodysplastic syndrome (MDS) is characterized by a heterogeneous hematopoietic disease, manifesting clinical and pathological changes due to inefficient cellular differentiation. This inefficiency causes a peripheral cytopenia, which uses as a parameter for the characterization of the disease. MDS is a very common disease in the western hemisphere and mostly affects the senile population. This association of MDS with age is linked to hematopoietic stem cell (CTH) quiescence caused by advancing age and senescence. Recent studies show the Klotho gene as an important biomarker for cancer associated with tumor cell proliferation and apoptosis. The clinical impact of Klotho on MDS is not yet defined. In this study, hypothetically, if an SMD pathogen can be affected by Klotho expression blockade, it reduces the production of reactive oxygen species (ROS) in the medullary microenvironment, attenuating CTH DNA damage and displaying cytopenic pictures, profile characteristic of the patients. To validate this hypothesis, a large case-control clinical study was performed with bone marrow samples from patients with MDS to show the different levels of α-Klotho (KL) and β-Klotho (KLB) genes expression, and how these genes may be associated with clinical laboratory variables of patients. Bone marrow tests were collected from 69 patients, distributed in 61 patients diagnosed with MDS at the tertiary hospital and 8 recommended controls. The cytogenetic study was performed by G-Band and analyzed the expression levels used by the real time PCR protocol (qRT-PCR). Among the variables analyzed, patients with increased expression levels in relation to the control group (p = 0.000), as well as the group of only one cytopenia or none compared to the group of two or three cytopenias (p = 0.001). ; which corroborates the form with the findings of hemoglobin and absolute neutrophil count (ANC) variables, in which the KL gene was more expressed in mild anemia levels (8-10 g / dL) in relation to anemia levels. (<8 g / dL) (p = 0.008) and in cases with favorable ANC (≥ 0.8 cells / mm³) compared to individuals with unfavorable ANC (<0.8 cells / mm³), second or IPSS-R (p = 0.008). In addition, KL was more expressed in female patients (p = 0.002) and in non-transfusion dependent patients (p = 0.001). The KLB gene showed no relationship between the variables and variables analyzed (p> 0.005). These approaches may define Klotho as a new pathological marker for MDS and improve advances in therapy.