Molecular analysis uncovers biological and diagnostic features in indolent and aggressive B-cell lymphomas with overlapping pathological aspects

Classifying B-lymphoproliferative processes can be a challenging task that significantly impacts patients' clinical diagnosis and treatment. Unfortunately, several types of these lymphomas remain unclassifiable using traditional methods. Therefore, we aimed to better understand the underlying pathobiological mechanisms by leveraging new-generation molecular technologies to ultimately help categorize these disorders more accurately. Thus, based on these open topics, the thesis's major aims can be divided into two main subjects on which we applied several types of molecular studies. One topic was the classification of Small B-cell lymphomas (SBCL) with unclear morpho-phenotypic features by incorporating NGS studies. Another project wanted to explore the differences between High-grade B-cell lymphomas with 11q aberrations (HGBL-11q) and Burkitt lymphoma (BL) based on the gene expression patterns to highlight important pathobiological aspects that can soon help to classify and differentiate HGBL-11q from other aggressive Germinal Center (GC) B-cell lymphomas. Concerning the SBCL project, through NGS analysis, we were able to distinguish Follicular Lymphoma from Mantle Cell lymphoma, while Marginal Zone lymphoma and Chronic Lymphocytic Leukemia were not easily classified even after applying advanced molecular technologies. In the second project, gene expression profiling detected that HGBL-11q and BL share a similar "early" GC Cell-of-origin profile, and we identified a group of genes that could potentially distinguish BL from HGBL-11q, facilitating the diagnosis in the future. Our research has concluded that new developments are needed in the classification of B-cell lymphomas. This can be achieved by incorporating more types of genomic studies and not just evaluating the morpho-phenotypic characteristics of the lymphoid populations. The primary goal is to achieve a comprehensive classification of lymphomas, which involves not only the morpho-phenotypic aspects but also an in-depth analysis of the molecular alterations to understand the true nature of the disease better.