These cases harbor alternate gene fusions or copy number alterations in ETS family transcription factors (ETV6, ERG, FLI1), IKZF1 or TCF3. ETV6-RUNX1-like ALL develops in children harboring germline ETV6 mutations with subsequent somatic alterations of the second ETV6 allele, consistent with the notion that biallelic alteration of ETV6 is central in leukemogenesis [124]. This evidence concerns the gene TCF3 and acute lymphoblastic leukemia.