CRLF2-rearranged ALL commonly has concomitant alterations that facilitate JAK-STAT signaling pathway activation, including sequence mutations of Janus kinases (most commonly at R683 of the pseudokinase domain of JAK2), IL-7RA, and deletions of negative regulators of JAK-STAT signaling (SH2B3 and USP9X) [246]. Here, CRLF2 is linked to acute lymphoblastic leukemia.