JAK/STAT signal transduction pathway in responses to hematopoietic growth factors. Under normal conditions (A), erythroid and megakaryocytic progenitors require binding of erythropoietin (Epo) or thrombopoietin (Tpo) to their respective receptors (Epo-R or Tpo-R) to initiate the intracellular sequence of phosphorylation and activation events leading to transcriptional activation of growth factor–responsive target genes (details presented in “Molecular mechanisms of PV and ET”). In hematopoietic progenitor cells of patients with MPDs who have the JAK2-V617F mutation (B), this JAK/STAT signal transduction pathway is constitutively activated in the absence of binding of Epo or Tpo to their respective receptors.