ABSTRACT
Abstract fhe transcription factors StatSa and Stat5b are crucial gene regulators for all hematopoietic cell types. StatS proteins play essential roles in hematopoietic stem cell maintenance as well as lineage commitment. Mutations in upstream molecules involved in controlling
Stat5 activity are frequendy observed in multiple forms of human leukemias, lymphomas or myelo-proliferative diseases. The main function of Stat5 is to promote proliferation and sur vival in all hematopoietic lineages in response to cytokine-and growth factor-induced signaling. Constitutive activation of StatS can result from activating mutations in upstream kinases or translocations generating fusion tyrosine kinases. Alternatively, persistent StatS activation can be associated with amplification of signaling molecules such as cytokines or growth factors and their cognate receptors. Here, we discuss normal StatS function in hematopoiesis, the role of StatS in transformation, consequences of full or partial deletion of StatS genes in transgenic mice and oncogenic gain-of-function mutants of StatS. We end on possible direct or indirect therapeutic intervention strategies involving the Jak-Stat signaling pathway.
