Several hypotheses have been raised regarding the impact of t(4;12) on AML pathogenesis: i) addition of deregulating enhancer elements near ETV6 region; ii) disruption of normal DNA binding function of ETV6 although keeping intact its homodimerization; and iii) interference or abolition of PRC2 binding sites near GSX2 locus leading to GSX2 overexpression. The gene discussed is GSX2; the disease is acute myeloid leukemia.