Project information
Microenvironmental Drivers of Aggressiveness and Therapy Resistance in Chronic Lymphocytic Leukemia

B cells form a central component of adaptive immunity, responsible for generating immune responses and immunological memory. Microenvironmental signaling governs these processes by directing B cell activation, proliferation, and differentiation. BCR signaling and other microenvironmental interactions are frequently dysregulated in leukemias and lymphomas derived from mature B cells, which exploit the pre-existing BCR-driven clonal expansion program. We propose to investigate whether transcription factors and other signaling molecules play a biological role in the (dys)regulation of the BCR pathway, using chronic lymphocytic leukemia (CLL) as a model disease.
Our objectives are: (1) to study the functional role of two selected transcription factors (TFs) in BCR signaling and in CLL-T cell interactions that activate malignant B cells, and to characterize their role in B–T cell interactions, which complement BCR activation in both normal and malignant B cells; (2) to assess whether these TFs contribute to therapeutic resistance to targeted therapy with BCR inhibitors or BCL2 inhibitors; (3) to test TF inhibition as a therapeutic strategy. Overall, this study aims to define the role of TFs in the (dys)regulation of BCR signaling and B–T cell interactions. Ultimately, this could lead to a better understanding of the pathophysiology of B cell-related diseases such as leukemias, and lymphomas.