In high-risk B-ALL, rearrangements of CRLF2 are frequently found together with IKZF1 alterations and activating mutations in JAK1 and JAK2, most commonly at or near R683 in the pseudokinase domain of JAK2 [40–42], and are associated with very poor outcome [46, 47]. This evidence concerns the gene CRLF2 and acute lymphoblastic leukemia.