Anti-apoptotic role of STAT5 in haematopoietic cells and in the pathogenesis of malignancies.

Signal Transducers and Activators of Transcription (STATs) are a family of proteins that mediate cytokine and growth factor induced signals playing a role in cell differentiation, proliferation, development, inflammation, and apoptosis. While other STATs can mediate pro-apoptotic or anti-apoptotic signals depending on the conditions of cell stimulation, STAT5 only demonstrates a pro-survival signal. The STAT5 induced cell survival promotion is due to regulation of transcription of genes that encode proteins which inhibit or trigger the cell death, such as the Bcl-2 family members or caspases. STAT5 is essential but not sufficient in the survival process. Signalling activators such as Ras and PI3-Kinase, cooperate with STAT5. Constitutive activation of STAT5 is associated with a wide variety of human malignancies, including leukaemia, breast, head and neck, and prostate cancers. Up-regulation of STAT5 target genes leads to changes of normal cellular growth and survival control mechanisms. Block of constitutive STAT5 activation could be a novel therapeutic approach to treat human malignancies.