Stat5a/b contribute to interleukin 7-induced B-cell precursor expansion, but abl- and bcr/abl-induced transformation are independent of Stat5

The cytokines interleukin 7 (IL-7) and interleukin 4 (IL-4) regulate lympho id differentiation and function and activate the transcription factor Stat5 , Using mice deficient for the 2 highly related transcription factors, Stat 5a and Stat5b (Stat5a/b(-/-)), we investigated the role of Stat5 for B-cell differentiation, expansion, and function. Peripheral blood B cells of Stat 5-deficient mice are significantly reduced, but no proliferation defects in response to various mitogenic stimuli are found. Also, IgM and IgG1 antibo dy production and immunoglobulin class switching are not affected. Pre- and pro-B cells of Stat5-deficient animals were found to have reduced response s to IL-7. Pro- and pre-B cells are the target cells of the abl oncogene an d numerous studies have suggested that Stat5a/b is essential for transforma tion by derivatives of the Abelson (abi) gene. To assess the role of Stat5a /b in transformation, we have evaluated the ability of various abl derivati ves to transform cells from Stat5a/b-deficient mice in vitro or in vivo. We demonstrate that the absence of Stat5a/b is not essential for the inductio n of lymphoid or myeloid tumors in vivo or on the ability to transform bone marrow cells in vitro. (Blood, 2000;96:2277-2283) (C) 2000 by The American Society of Hematology.