Human MLL/KMT2A gene exhibits a second breakpoint cluster region for recurrent MLL–USP2 fusions

For nearly 3 decades, the human MLL (KMT2A) gene and its rearrangements have been investigated in many different laboratories around the world. At our diagnostic center (DCAL Frankfurt), our standard strategy for the identification of MLL -r is based on two independent approaches, namely “Multiplex” (MP)-polymerase chain reaction (PCR) and “Long distance inverse” (LDI)-PCR approach [ 1 ]. The MP-PCR approach is used to rapidly identify the eight most frequent MLL fusions ( AF4 , AF6 , AF9 , AF10 , ENL , ELL , EPS15 , and PTDs ) which encompass ~90% of all diagnosed MLL -r leukemia patients, while LDI-PCR is used for all other patients (~10%). By applying both technologies, we have accumulated 94 direct MLL- gene fusions and 247 reciprocal fusion partner genes [ 2 ]. Nearly, all breakpoints have been identified in the major breakpoint cluster region (BCR) of the MLL gene ( MLL exons 8–14). However, some of the patients remained negative, although they were positively prescreened by various methods.