STAT5-mediated self-renewal of normal hematopoietic 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 toward differentiation might exhaust the stem cell pool, while a shift toward 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 might contribute to the development of human leukemias.
Department of Experimental Hematology; University Medical Center Groningen; Groningen, The Netherlands ; Department of Stem Cell Biology; University Medical Center Groningen; Groningen, The Netherlands.
Hein
H
Schepers
Albertus T J
AT
Wierenga
Edo
E
Vellenga
Jan Jacob
JJ
Schuringa
cell type-specific signaling; human hematopoietic stem cells; leukemia; leukemic transformation; self-renewal