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University of Rochester Medical Center
Integrin and Chemokine-Mediated Homing During B Cell Ontogeny and Leukemogenesis
Acute lymphoblastic leukemia is a form of cancer that affects the lymphocytes and lymphocyte-producing cells in bone marrow. B-lymphocytes (B-cells for short) are white blood cells that produce antibodies and are vital parts of the body's immune system. Acute lymphoblastic leukemia often affects B-cells and the precursor cells that mature into B-cells. As our knowledge of blood cell formation grows, it is clear that normal hematopoietic cells (cells involved in blood formation) are influenced by regulatory signals derived from special "micro-environments" within the bone marrow. Without these signals, normal blood cells cannot grow and survive. There is increasing evidence that leukemic cells respond to similar regulatory signals in the bone marrow that may influence how they grow, survive, and migrate to other tissues as part of the disease process. Dr. Fay Young is proposing to use a unique mouse model to study the roles of integrin (a substance that promotes adhesion of cells, which is characteristic of some cancers) and signalling molecules known as chemokines in the transformation of B-cell precursors into leukemic cells. Specifically, she will study the relationship between genetic alterations in mice, expression of chemokines and surface adhesion receptors (which facilitate adhesion), and the development of leukemia.