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 lymphoid acute leukaemia. The gene is commonly involved in reciprocal translocations leading to the creation of chimaeric genes encoding novel protein products. 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 that partial duplications of the MLL gene are detectable in peripheral blood and bone marrow of healthy donors and in normal non- haemopoietic tissues. Sequence analysis of the 45 kb of the 5' end of the MLL locus encompassing the breakpoints of these genomic duplications has failed to show a definitive 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 apparent Alu-mediated homologous recombination, several joins do not involve Alu elements in the region, despite a high density of these repetitive elements in the sequence.