Lymphocyte Development & Leukemogenesis

Research in the Lymphocyte development and Leukemogenesis Laboratory focuses on T lymphocyte development, both under steady state, physiological conditions, as well as in leukemia.

 

T lymphocyte development occurs mostly in the thymus from progenitors of bone marrow origin in a process that involves high cellular turnover. Our former work found that thymus turnover is regulated by cell competition. Specifically, the seeding of the thymus by ‘young’ hematopoietic precursors (with a short dwell time in the thymus) led to the clearance of the ‘old’ precursors (residing for longer in the thymus).

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Importantly, cell competition is not cell autonomous, i.e., it is the presence of the young that induce the clearing of the old. Consistently, when no progenitors seed the thymus, i.e., if no cell competition takes place, old precursors persist in the thymus, self renew, and for some time give rise to T lymphocytes. In other words, autonomously maintain thymus function. Nevertheless, while apparently beneficial for a short period, prolonged thymus autonomy led to aggressive T cell acute lymphoblastic leukemia with strong similarities with the human disease. The Lymphocyte development and Leukemogenesis Laboratory focuses on the identification of the cellular and molecular mechanisms governing cell competition in normal thymus turnover, and on the changes associated with the malignant transformation of T lymphocyte precursors as a consequence of impaired cell competition.