STAT 5 - Mediated Self-Renewal of Normal and Leukemic Stem Cells
The level of transcription factor activity critically regulates cell fate decisions such as hematopoietic stem cell self‑renewal and differentiation. The balance between hematopoietic stem cell self‑renewal and differentiation needs to be tightly controlled, as a shift towards differentiation might exhaust the stem cell pool while a shift towards self‑renewal might mark the onset of leukemic transformation. A number of transcription factors have been proposed to be critically involved in governing stem cell fate and lineage commitment, such as HOX transcription factors, c‑Myc, Notch1, β‑Catenin, C/EBPα, PU.1 and STAT5. It is therefore no surprise that dysregulation of these transcription factors can also contribute to the development of leukemias. This review will discuss the role of STAT5 in both normal and leukemic hematopoietic stem cells as well as mechanisms by which STAT5 can contribute to the development of human leukemias.