The first-in-class JAK1/JAK2 inhibitor ruxolitinib inhibits JAK/STAT signaling, 
inducing durable reductions in splenomegaly and constitutional symptoms in 
patients with myelofibrosis. However, the association of ruxolitinib therapy 
with myelosuppression indicates the continued need for optimal treatment choices 
in myelofibrosis. Pacritinib, a dual JAK2 and FLT3 inhibitor, improves 
disease-related symptoms and signs with manageable gastrointestinal toxicity in 
patients with myelofibrosis with splenomegaly and high-risk features, without 
causing overt myelosuppression, and therefore may provide an important treatment 
option for a range of patients with myelofibrosis. This article examines the 
role of JAK2 and FLT3 signaling in myelofibrosis and provides an overview of the 
clinical development of pacritinib as a new therapy for myelofibrosis.