Experimental oncology

B-Cell Neoplasia

Group leader

Paolo Ghia

Unit research activity is aimed at understanding the molecular mechanisms responsible for the onset and progression of B cell lymphoproliferative disorders (leukemia and lymphomas), which represent most of the neoplasms of the immune system, accounting for 10% of all types of cancer. To this aim, the Unit intends to identify molecules and signal transduction pathways relevant to leukemic progression and that can potentially be used as diagnostic markers, prognostic factors or new potential therapeutic targets. To this end, research methodology is based on the integration of experimental results obtained, in vitro and in vivo, from the study of normal and neoplastic B lymphocytes.

This approach originates on the evidence that a better understanding of the physiological mechanisms of the immune system is essential to achieve a deeper understanding of the process of neoplastic transformation of B lymphocytes.

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Research activity

The research activity of B cell Neoplasia Unit is focused on the fundamental role played by the microenvironment in the pathogenesis of CLL by studying the surrounding non-neoplastic cells and the molecular interactions occurring with the leukemic clone that are responsible for the survival and expansion of the leukemia. Particular attention is given to the definition of the role played by the antigen receptor (B Cell Receptor- BcR) and its interaction with foreign or self antigens, with the final goal of interfering with the receptor activation. Sustained activation of downstream signaling pathways may occur and represent novel vulnerabilities currently exploited as therapeutic targets.

The role of the BcR but also of genetic aberrations is explored also in the context of Monoclonal B lymphocytosis (MBL) a pre-leukemic condition originally described by the Unit that provides a unique model to study the initial steps of tumor progression, including antigen-like stimulations.

The experimental work is performed on both animal models of the disease (xenotransplants in immunodeficient mice, genetically modified animals) but in particular on primary leukemic cells obtained from patients followed at the Strategic Research Program in CLL at our hospital, directed by the head of Unit, Paolo Ghia, where specialized clinicians design and conduct innovative interventional clinical trials but also prospective and retrospective observational studies.

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