The role of Janus kinases in haemopoiesis and haematological malignancy

The production of blood cells is regulated by a number of protein growth factors and cytokines that influence cell survival, proliferation and differentiation. Many of these molecules bind to cell surface receptors, which belong to a family of closely related cytokine receptors that lack intrinsic catalytic activity but are intimately associated with tyrosine kinases of the Janus kinase (JAK) family. Ligand binding induces the activation of JAKs, which sit at the apex of a signalling cascade in which a key role is played by members of the signal transducers and activators of transcription (STAT) group. Congenital deficiencies in JAK-STAT signalling are associated with immunodeficiency states and acquired activating mutations and translocations are involved in the pathophysiology of haematological malignancy. The latter findings have raised hopes that drugs that target aberrant JAK-STAT signalling may be useful for the treatment of human disease.