description). This 11A2 application will employ the ML-1 human myeloblastic leukemia cell line to study the molecular responses to specific growth versus differentiation cytokines this laboratory has identified in this model. These include phospholipid pathways and lipid-derived second messengers formed from them; the role of the c-ets-1 protein in regulating c-myb expression; the type and level of cell cycle regulating proteins such as cyclins, cyclin-dependent kinases and tumor repressors. In addition experiments are proposed to examine the effect of these cytokines on differentiation in bone marrow from patients with AML in the presence of specific antitumor agents.
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