RESUMEN
Systemic lupus erythematosus (SLE) is a chronic, heterogeneous, systemic autoimmune disease characterized by autoantibody production, complement activation, and immune complex deposition. SLE predominantly affects young, middle-aged, and child-bearing women with episodes of flare-up and remission, although it affects males at a much lower frequency (female: male; 7:1 to 15:1). Technological and molecular advancements have helped in patient stratification and improved patient prognosis, morbidity, and treatment regimens overall, impacting quality of life. Despite several attempts to comprehend the pathogenesis of SLE, knowledge about the precise molecular mechanisms underlying this disease is still lacking. The current treatment options for SLE are pragmatic and aim to develop composite biomarkers for daily practice, which necessitates the robust development of novel treatment strategies and drugs targeting specific responsive pathways. In this communication, we review and aim to explore emerging therapeutic modalities, including multiomics-based approaches, rational drug design, and CAR-T-cell-based immunotherapy, for the management of SLE.
Asunto(s)
Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/terapia , Lupus Eritematoso Sistémico/inmunología , Femenino , Biomarcadores , Inmunoterapia/métodos , MasculinoRESUMEN
While considerable information exists on the ten-eleven translocation 2 (TET2) mutational landscape in AML, the information on TET2 expression is limiting. So, we aimed to study the TET2 expression at mRNA and protein levels in AML patients compared to healthy controls. To achieve this, we recruited 70 non-M3, de novo AML patients and 20 healthy controls. The expression of TET2 was checked at mRNA and protein levels by qPCR and ELISA respectively and the TET activity was checked by the 5-hmC assay. TET2 mRNA expression was correlated with clinicopathological parameters and overall survival. We found a significant downregulation of TET2 mRNA and protein and significantly lower DNA 5-hmC levels in AML patients compared to controls. TET2 downregulation was more in patients with high blast counts and patients of the adverse-risk ELN category. We also found a significant upregulation of DNMT1 and DNMT3a suggesting a hypermethylation phenotype in de novo AML.