Interleukin (IL)-2 and IL-4 are important for the growth of human primary B cells. These cytokines activate signal transducer and activator of transcription (STAT) 5. However, the role of STAT5 in normal human B cell growth is not completely clear. Our preliminary data suggest that activation of STAT5 promotes survival of normal human B cells. STAT5 is known to regulate expression of anti-apoptotic Bcl-xL. We, therefore, propose that STAT5 prevents normal B cell apoptosis through upregulation of Bcl-xL. In the first aim of this proposal we will investigate whether STAT5 supports B cell growth through inhibition of apoptosis by using overexpression and RNA interference approaches. In the second aim of this proposal we will investigate whether STAT5 can regulate B cell apoptosis through upregulation of Bcl-xL and we will determine the requirement for Bcl-xL in STAT5-mediated protection from apoptosis. Lastly we will identify new STAT5-regulated anti-apoptotic genes in addition Bcl-xL through RT-MLPA, a novel gene expression analysis method. Findings from this proposal will provide insight into the control of normal human B cell growth and may provide new targets for treatment of B cell malignancies. ? ?
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