Stat5 as Hematopoietic Gatekeeper and Oncogene Upon Tyrosine Kinase‑Induced Transformation
Katrin Friedbichler, Marc A. Kerenyi, Ernst W. Müllner and Richard Moriggl
The transcription factors Stat5a and Stat5b are crucial gene regulators for all hematopoietic cell types. Stat5 proteins play essential roles in hematopoietic stem cell maintenance as well as lineage commitment. Mutations in upstream molecules involved in controlling Stat5 activity are frequently observed in multiple forms of human leukemias, lymphomas or myelo‑proliferative diseases. The main function of Stat5 is to promote proliferation and survival in all hematopoietic lineages in response to cytokine‑ and growth factor‑induced signaling. Constitutive activation of Stat5 can result from activating mutations in upstream kinases or translocations generating fusion tyrosine kinases. Alternatively, persistent Stat5 activation can be associated with amplification of signaling molecules such as cytokines or growth factors and their cognate receptors. Here, we discuss normal Stat5 function in hematopoiesis, the role of Stat5 in transformation, consequences of full or partial deletion of Stat5 genes in transgenic mice and oncogenic gain‑of‑function mutants of Stat5. We end on possible direct or indirect therapeutic intervention strategies involving the Jak‑Stat signaling pathway.