Although the precise mechanism of B-ALL predisposition remains to be determined, it is striking to observe that germline variants have been identified in genes regulating cell growth and death (TP53 and CDKN2A) (84, 91), as well as in genes encoding proteins implicated in B cell development (ETV6, IKZF1, NBN, TCF3, TRAF3IP3, and PAX5) (21, 85, 86, 87, 88, 90, 92), regulation of cytokine signaling (SH2B3) (89), and ubiquitination (USP9X) (93). The gene discussed is IKZF1; the disease is acute lymphoblastic leukemia.