Fig 2.

Regulation of haematopoiesis by the erythropoietin (EPO) and thrombopoietin (TPO) receptors (EPO-R and TPO-R). The erythrocyte and platelet growth factors erythropoietin and thrombopoietin stimulate cell growth by binding cell surface receptors on haematopoietic progenitor cells. Receptor ligation leads to phosphorylation of the JAK2 tyrosine kinase and recruitment and activation of STATs. Activated, dimerised STATs pass into the nucleus, where they regulate the expression of genes that are required for cell-cycle activation and cell proliferation. Mutations in the JAK2 gene that result in constitutive activity are associated with PV, ET and PMF. Mutations in the MPL gene, coding for the TPO-R, are found in ET. CML = chronic myeloid leukaemia; EPO = erythropoietin; ET = essential thrombocythaemia; JAK2 = Janus-associated kinase 2; MPL = myeloproliferative leukemia; P = phosphorous; PMF = primary myelofibrosis; PV = polycythaemia vera; STAT = signal transducers and activators of transcription; TPO = thrombopoietin.