Figure 1.

Schematic of JAK-STAT signaling and activating tyrosine kinase gene mutations in myeloproliferative neoplasms (MPNs).

(a) Cytokine-receptor binding (e.g. TPO/MPL) leads to JAK2 activation, followed by recruitment and phosphorylation of STAT proteins, which then translocate to the nucleus and activate transcription of genes involved in proliferation and survival.

(b) Activating mutations in tyrosine kinases (e.g. MPL, JAK2) lead to JAK-STAT activation in the absence of cytokine stimulation.