Supervisors info:
Αγαθαγγελίδης Ανδρέας, Επίκουρος Καθηγητής Γενετικής - Μοριακής Γενετικής Ευκαρυωτικών Οργανισμών, Τμήμα Βιολογίας, ΕΚΠΑ
Summary:
Chronic Lymphocytic Leukemia (CLL) is a neoplasm of mature B cells. The clinical course of patients is highly heterogeneous, while at the biological level the disease results from a combination of genetic factors and components of the cellular microenvironment. In most patients, white blood cell counts show minimal changes over time and the disease can remain stable for years. In others, disease progression may be significantly faster, directly depending on the proliferation rate of leukemic cells. In this context, the identification of molecular biomarkers - such as gene mutations and quantitative analysis of gene, protein, and other molecule expression - supports the diagnosis, staging, and prognosis of the disease. Data indicate that the clonotypic B-cell receptor (BcR) plays a central role in the pathophysiology of CLL, as continuous interaction between the leukemic clone and the microenvironment via the BcR induces phenotypic and functional divergence.
The aim of this study was to explore novel biomarkers through the standardized analysis of immunoglobulin molecules of the clonotypic BcR in patients with CLL. Specifically, PCR amplification of the BcR immunoglobulin molecules was performed in a series of CLL patients, followed by structural analysis using modern bioinformatics tools. Based on the structural data, patients were subsequently grouped with the ultimate goal of improving their molecular classification.
The structural classification of the clonotypic BcR immunoglobulins could provide important information on the biology and prognosis of CLL. The present study led to the identification of groups of patients with BcRs that are structurally shaped by distinct immunogenetic characteristics, such as the rearranged IGHV gene and the somatic hypermutations status, which appear to be important for the process of antigenic selection and, therefore, the clonal evolution of the disease. This approach is expected to contribute to a deeper understanding of the pathogenesis of CLL and the development of targeted therapeutic interventions.
Keywords:
Chronic Lymphocytic Leukemia, B Cell Receptor, Biomarkers, Structural Analysis, Immunoglobulins
