MLL Breakapart Probe

Rearrangement of the MLL gene at chromosome band 11q23 can be detected in the leukaemia cells of approximately 85% of infants with B-ALL. Translocations involving the MLL (11q23) gene are generally associated with increased risk for treatment failure. The most frequently observed of these translocations is the t(4;11) translocation involving the MLL gene and the AF4 gene on chromosome. The poor outcome for infants with ALL is strongly associated with the presence of this rearrangement in particular. The discovery that a single YAC spanned breakpoints in four of the more common translocations led to the naming of a candidate gene, MLL (Myeloid/Lymphoid or Mixed Lineage Leukaemia). The gene has homology with a drosophila gene (‘trithorax‘), which is highly conserved in humans, and gives rise to a protein that can be folded to give six zinc finger domains and is a developmental regulator. The zinc finger domains are translocated to the AF4, AF9 and ENL1 genes respectively on the partner chromosomes in the t(4:11), t(9:11) and t(11;19) translocations. Each of the genes involved in these translocations have been shown to have high sequence homology. The MLL gene is necessary to maintain HOX gene expression, which is an important gene involved in development. The fusion genes have a different mechanism to the native protein and do not have the same effect.

The MLL probe mix has a green 5’ probe and a red 3’ probe. The 3’ region probe (96kb) spans the CDG3 gene and 16kb of the UBE4A gene whilst the 3’ region probe (87kb) spans a region 3’ of exon 5.