Stat5 as a Hematopoietic Master Regulator for Differentiation and Neoplasia Development

Stat5 transcription factors have a crucial role in hematopoiesis from hematopoietic stem cells to fully differentiated cells. The individual contributions of Stat5a and Stat5b genes to the generation of hematopoietic cells and to their malignant transformation are subject of the following review. Absence of Stat5 proteins causes lymphopenia and Stat5 was recognized to be indispensable for the development of B-, T- and NK-cells. The few peripheral T-cells that develop in Stat5-deficient mice have an activated phenotype and these T-cells contribute to the development of autoimmunity. Moreover, deletion of Stat5 in myeloid cells causes myelodysplasia (red cell anemia and thrombocytopenia). In addition, generation and function of mast cells and eosinophils depends on Stat5. Impoartantly, Stat5 was found to be highly expressed and constitutively activated in many human hematopoietic neoplasms, where it regulates expression of genes controlling cell survival and cell cycle progression. Expression of Stat5 in hematopoietic neoplasms was both found to be elevated at the mRNA and protein level. Interestingly, higher Stat5 levels were linked with tyrosine kinase inhibitor drug resistance.