Analysis of the region of the 5 ' end of the MLL gene involved in genomic duplication events

Rearrangements of the MLL gene are associated with both myeloid and lymphoi d acute leukaemia, The gene is commonly involved in reciprocal translocatio ns leading to the creation of chimaeric genes encoding novel protein produc ts. An alternative mechanism of MLL gene rearrangement is due to intragenic duplication, leading to partial duplication of the amino-terminal portion of the protein. This occurs in leukaemia, but it has recently been shown th at partial duplications of the MLL gene are detectable in peripheral blood and bone marrow of healthy donors and in normal non-haemopoietic tissues. S equence analysis of the 45 kb of the 5' end of the MLL locus encompassing t he breakpoints of these genomic duplications has failed to show a definitiv e reason as to why this region is such a frequent target of rearrangement. Indeed, although the majority of the breakpoint joins are the result of app arent Alu-mediated homologous recombination, several joins do not involve A lu elements in the region, despite a high density of these repetitive eleme nts in the sequence.