However, this cellular response requires tight regulation, as aberrant signaling has been unequivocally linked to mutations in key signaling genes, such as the valine 617 mutation in the JAK2 pseudokinase (JH2) domain associated with myeloproliferative disease [6], and the JAK1- and JAK2-activating mutations associated with acute lymphoblastic leukemia (ALL) [4], [5]. This evidence concerns the gene JAK2 and acute lymphoblastic leukemia.