Cytokines, such as interleukins and thrombopoietin, control the development and physiology of hematopoietic lineages and aberrant cytokine signalling has been associated with the initiation and/or progression of leukemias. Upon binding of cytokines to their respective receptors several signalling pathways are activated that elicit various cellular responses, including proliferation, differentiation, survival and death. The majority of cytokines activate pathways that utilize the transcription factors Stat5a and Stat5b (Stat5). In fact, aberrant activation of Stat5 has been observed in leukemias, which suggests that it plays a critical role in disease progression. Deletion of the transcription factor Stat5 from the mouse genome results in multiple defects in many organ systems, emphasizing a crucial role of cytokines in a number of different cell types. Researchers in LGP in collaboration with other scientists have used mice from which the Stat5 genes had been deleted either from the germline or from specific cell types to explore the mechanisms by which Stat5 controls normal and neoplastic hematopoiesis. Our findings demonstrated a critical role of Stat5 in the function of the immune system (B and T cells) and in some myeloid disorders. ? ? Recent findings demonstrated that the transcription factor Stat5 is essential for the development of myeloproliferative disease induced by the TEL-PDGFRB translocation, wich suggests that inhibitors against Stat5 might be suitable approach to treat various forms of leukemias. Other findings demonstrated that Stat5 is critical for early B cell development and accurate generation of T helper cells.

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Zhu, Bing-Mei; McLaughlin, Sara K; Na, Risu et al. (2008) Hematopoietic-specific Stat5-null mice display microcytic hypochromic anemia associated with reduced transferrin receptor gene expression. Blood 112:2071-80
Hennighausen, Lothar; Robinson, Gertraud W (2008) Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B. Genes Dev 22:711-21
Liu, Fulu; Kunter, Ghada; Krem, Maxwell M et al. (2008) Csf3r mutations in mice confer a strong clonal HSC advantage via activation of Stat5. J Clin Invest 118:946-55
Laurence, Arian; Tato, Cristina M; Davidson, Todd S et al. (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26:371-81
Yao, Zhengju; Kanno, Yuka; Kerenyi, Marc et al. (2007) Nonredundant roles for Stat5a/b in directly regulating Foxp3. Blood 109:4368-75
Le, Yi; Zhu, Bing-Mei; Harley, Brendan et al. (2007) SOCS3 protein developmentally regulates the chemokine receptor CXCR4-FAK signaling pathway during B lymphopoiesis. Immunity 27:811-23
Cain, Jennifer A; Xiang, Zhifu; O'Neal, Julie et al. (2007) Myeloproliferative disease induced by TEL-PDGFRB displays dynamic range sensitivity to Stat5 gene dosage. Blood 109:3906-14
Villarino, Alejandro V; Tato, Cristina M; Stumhofer, Jason S et al. (2007) Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals. J Exp Med 204:65-71
Dai, Xuezhi; Chen, Yuhong; Di, Lie et al. (2007) Stat5 is essential for early B cell development but not for B cell maturation and function. J Immunol 179:1068-79