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Scientists investigate non-coding parts of the genome and their impact on leukaemia and lymphoma

Thanks to the EXPRO grant, Marek Mráz from CEITEC MU and the University Hospital Brno will investigate the importance of non-coding RNAs in cancers arising from B lymphocytes.

Marek Mráz.

Adaptive immunity, which generates an immunological response, works primarily through B lymphocytes, whose proliferation and differentiation are controlled by so-called B cell receptors (BCRs). Signalling through BCRs is crucial for the body's immune responses, and disruption of these can lead to leukaemias or lymphomas or autoimmune diseases.

Scientists have been studying what all influences the BCR signaling pathway and its regulation for many years. In his new project, Marek Mráz wants to focus on whether long non-coding RNAs (lncRNAs) also play a biological role in this process.

"LncRNAs are RNA molecules that do not encode proteins but may play a key role in regulating cell (patho)physiology. They represent the largest class of human genes, but their functions are still poorly characterized. They have highly tissue-specific expression and can influence a variety of cellular processes, including signalling pathways," Mráz described the importance of these molecules.

Thanks to the new EXPRO grant, he and his colleagues will try to identify those lncRNAs that regulate BCR signalling in normal and malignant B cells. In fact, they believe that long non-coding RNA molecules may contribute to the development of chronic lymphocytic leukaemia, the most common type of leukaemia in adults. Mráz speculates that lncRNAs may also influence treatment resistance and other processes in the tumor microenvironment, such as the interaction between B cells and T cells, which are also involved in the aggressiveness of B cell-derived cancers.

The aim of the project is to investigate the functional role of three selected long non-coding RNA molecules in BCR signaling pathway and activation of malignant B cells. The researchers will also investigate a new mouse model created to study the role of lncRNAs in adaptive immunity and aim to characterize the role of lncRNAs in B cell-T cell interactions.

"Ultimately, all of this could lead to a better understanding of the pathophysiology of B cell-related diseases such as leukaemias or lymphomas or autoimmune disorders, potentially identifying new targets for the treatment of these diseases," Mráz added.