We are the first to show that CRLF2 is a direct target of IKZF1, that IKZF1 regulates CRLF2 expression, and that restoration of IKZF1 activity using the CK2 inhibitor, TBB, can suppress CRLF2 expression via chromatin remodeling in ALL. Here, CRLF2 is linked to acute lymphoblastic leukemia.