One of the reasons arguing against the contact first hypothesis was that 3D-FISH analysis indicated closer spatial proximity of MLL and ENL genes in interphase nuclei of myeloid (AML-193, PLB-985) and lymphoid cells (Nalm-6, IM-9) as compared with MLL and AF4 genes, even though AF4 represents the most frequent partner in MLL translocations (Gué et al., 2006). This evidence concerns the gene AFF1 and acute myeloid leukemia.