Determination of new biomarkers by comparative proteomic analysis of chronic lymphocytic leukemia B cells and normal B cells

Chronic Lymphocytic Leukemia (CLL) is a heterogeneous B cell carcinoma that is the most common type of adult leukemia in western countries with a broad clinical spectrum. Genomic changes have been reported to a large extent in CLL patients and genomic-transcriptomic techniques have been used as a basic tool to study aspects of the treatment, prognosis, classification and progression of the disease. However, further studies are needed on proteomic approaches since gene expression does not always represent the expression of proteins in B cell. In this thesis, we aimed to determine the biomarkers that can be used in the diagnosis and treatment, new drug targets and metabolic pathways in which these proteins are effective by identifying the proteomic level differences between the KLL patient and the B cell samples of the intact individuals by using DNA-based protein affinity reagents by comparative proteomics analyzes. 1129 protein was investigated with proteomic test platform and it was determined that the expression level of 132 protein significantly changed. Among these proteins, The most significant decreased and increased proteins were validated by molecular tests. The findings showed that there was a significant difference in proteome differences between CLL patients and intact B cell samples. It has been determined that SPOCK2, GZMH, GNLY, ANXA1, LTA4H, CST2, CST6, PROS1, F9 and THBS1 proteins were found to be candidates for biomarkers in the diagnosis of CLL, mainly APOE4 and ACY1. among proteins that change most significantly with the analyzes. In addition, the differences in expression levels of proteins have shown that CLL disease may be associated with changes associated with LXR/RXR signaling pathway and platelet mechanism by the use of different bioinformatics tools.