NK CELL ROLE IN RESISTANCE TO LEUKEMIA

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The overall aim of this proposal is to study natural killer (NK) cells' role in the course of leukemic disease, and their regulatory activity over proliferation and differentiation of normal hemopoietic cells in man. Specifically, we plan to investigate peripheral blood NK-cell anti-leukemia reactivity of normal donors and leukemic patients with active disease and in remission against: (1) freshly derived clonogenic leukemia cells in clonogenic assay for leukemic cell growth in vitro, and (2) against heterogeneous population of leukemia cells in a single cell assay, 51chromium-release assay, and competitive inhibition assay. We will further investigate the relationship between the stage of leukemic cell differentiation (as determined by morphological, phenotypic cytochemical, and cytogenetic criteria) and their sensitivity to NK cell attack. The mechanism(s) of NK-cell anti-leukemia reactivity will be also studied. Endogenous and activated NK cells will be tested. NK cells will be activated primarily by interleukin-2 and various species of interferons. We will also study the effect of cloned NK cells (or the cytotoxic factor from these cells) from normal donors and patients with leukemia to mediate anti-leukemia effect. Since leukemia is a disease of hemopoietic system and NK cells have been shown to exert regulatory activities over hemopoiesis, it is imperative to study the mechanism of NK-cell regulatory functions over growth and differentiation of normal hemopoietic progenitors. The effect of NK cells on the following hemopoietic progenitors will be studied: GM-CFC, BFU-E, and GMME-CFC. These studies may provide insight into the mechanism of disregulation of hemopoiesis in leukemia, and may lead to the development of new protocols for treatment of leukemia-diseased patients. (IS)