Figure 1.

Mechanisms of resistance to Janus kinase 2 (JAK2) inhibitors. Resistance to JAK2 inhibition may develop via acquisition of JAK2 resistance mutations (genetic resistance) or via the formation of JAK family heterodimers of JAK2 with JAK1 or tyrosine kinase 2 (TYK2), which functionally sustain downstream signaling (adaptive resistance). Intrinsic resistance to JAK2 inhibition may relate to compensatory activation of downstream signaling pathways as, for example, the mitogen-activated protein kinase (MAPK) pathway due to bypass activation via receptor tyrosine kinases as, for example, platelet-derived growth factor receptor. The figure was created with BioRender. PI3K = phosphoinositide 3-kinase; STAT = signal transducer and activator of transcription.