MGUS'ta azalmış GADD45A gen ifadesi seviyesi

Abstract

Purpose: Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia. It is known that MGUS has an increased risk of progression to multiple myeloma (MM), and also prepares the ground for diseases such as Waldenstrom macroglobulinemia (WM), non-Hodgkin lymphoma, and chronic lymphocytic leukemia (CLL). Our study aimed to evaluate whether some important p53 pathway genes differ in terms of expression in MGUS and healthy individuals. Materials and methods: For the study, bone marrow was collected from 8 healthy individuals and 8 individuals diagnosed with MGUS, and RNA samples were isolated. Expression levels of various genes involved in the p53 pathway were compared using the RT2-profiler PCR array. β-actin housekeeping gene expression level was used for normalization. The Pearson Correlation analysis and Receiver Operating Characteristic (ROC) analysis were conducted. Results: Among the genes whose expression levels were examined in this study, it was determined that the expression level of only the GADD45A gene decreased significantly in MGUS compared to the control group (p=0.027). Pearson correlation data showed that GADD45A gene expression was highly correlated with 12 of the other genes (APAF1, CDK4, PCNA, BAX, CDKN2A, CASP9, CHECK2, MDM2, RB1, P53, BCL2, CHEK1) examined in the p53 pathway (r>0.7). In addition, according to the ROC analysis, GADD45A is detected to have a strong discrimination power between MGUS and healthy individuals (AUC=0.797 and p=0.015). Conclusion: The decreased expression of the GADD45A gene in the MGUS group compared to the control group may be useful as a new biomarker to detect the risk of progression from MGUS to MM.