Thus, tyrosine-phosphorylated JAK2-V617F accumulates in the presence of ruxolitinib in the intermediate active kinase conformation [49], which leads to a drastic activation of JAK2-V617F upon removal of ruxolitinib to cause the severe withdrawal syndrome observed specifically in JAK2-V617F-positive MPN patients with abruptly discontinued ruxolitinib [30]. Here, JAK2 is linked to myeloproliferative disorder.