Interestingly, CRLF2/JAK2 mutant B-ALL cells with sustained depletion/inhibition of JAK2 generated a “neo-dependency” on c-Myc signaling, shown through the enhanced sensitivity of these cells to both RNAi-mediated depletion of c-Myc and the BET bromodomain inhibitors iBET151 and JQ1. Here, CRLF2 is linked to acute lymphoblastic leukemia.