Evidence from both neonatal blood spots and monochorionic twins of ETV6-RUNX1 ALL cases, supported by deep sequencing, has demonstrated that ETV6-RUNX1 frequently arises in utero, is unequivocally an initiating event (Greaves, 2003, Papaemmanuil et al., 2014), and occurs at high frequency, with approximately 1% of neonates harboring this first-hit translocation (Mori et al., 2002). This evidence concerns the gene RUNX1 and acute lymphoblastic leukemia.