Pre-B cell receptor signaling in acute lymphoblastic leukemia. B lymphocytes are not only the cells that produce antibodies as part of the human immune system, they are also the cell of origin in most cases of acute lymphoblastic leukemia (ALL). ALL represents by far the most frequent type of cancer in children and is also a common disease in adults. For many years, patients with ALL are treated with chemotherapy and current treatment protocols lead to cure rates of 80 percent for children and 55 percent for adult patients with ALL. Our goal is to better understand the biology of human ALL, namely as a catastrophic aberration of normal B lymphocyte development. During normal B lymphocyte development, the pre-B cell receptor represents a critical signaling unit that guides early B lymphocyte precursors on their path of maturation. If signaling from the pre-B cell receptor is compromised, as for instance in patients with innate immune defects, the B lymphocyte precursors are arrested in their development at a primitive stage -as in ALL cells. Therefore, we propose to investigate the function of the pre-B cell receptor signaling unit (1) as a potential target to disrupt aberrant cell signaling that promotes leukemic growth and (2) to restore normal pre-B cell receptor signaling in the leukemia cells.