No study has assessed whether the higher frequency of PML-RARA bcr1, involving the PML intron 6 in both de novo and t-APL, or the hotspots on intron 6 identified in t-APL, result from intrinsic sequence-specific properties per se, or from some selected random events that lead to leukemia. The gene discussed is RARA; the disease is acute promyelocytic leukemia.