ABSTRACT
Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested caseâcontrol study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.
ABSTRACT
Regulated cell death (RCD) plays a crucial role in the initiation and progression of tumors, particularly in acute myeloid leukemia (AML). This study investigates the prognostic importance of RCD-related genes in AML and their correlation with immune infiltration.We combined TCGA and GTEx data, analyzing 1488 RCD-related genes, to develop a predictive model using LASSO regression and survival analysis. The model's accuracy was validated against multiple databases, examining immune cell infiltration, therapy responses, and drug sensitivity among risk groups. RT-qPCR confirmed MT1E expression in AML patients and healthy bone marrow. CCK8 and Transwell assays measured cell proliferation, adhesion, migration, and invasion, while flow cytometry and Western blotting assessed apoptosis and protein expression.We developed a prognostic model using 10 RCD methods, which demonstrated strong predictive ability, showing an inverse correlation between age and risk scores with survival in AML patients. Functional enrichment analysis of the model is linked to immune modulation pathways. RT-qPCR revealed significantly lower MT1E expression in AML versus healthy bone marrow (p<0.05). Consequently, experiments were designed to assess the function of MT1E overexpression.Findings indicated that MT1E overexpression showed it significantly reduced THP-1 cell proliferation and adhesion(p<0.001), decreased migration(p<0.001) and invasiveness(p<0.05), and increased apoptosis(p<0.05), with a notable rise in Caspase3 expression.A novel AML RCD risk model was developed, showing promise as a prognostic marker for evaluating outcomes and immune therapy effectiveness. Insights into MT1E's impact on AML cell proliferation and apoptosis open possibilities for improving patient outcomes and devising personalized treatment strategies.
