MLL Breakapart - Detail

Rearrangement of the MLL gene at chromosome band 11q23 can be detected in the leukaemia cells of approximately 85% of infants with B-ALL^1,2,3. Translocations involving the MLL (11q23) gene are generally associated with increased risk for treatment failure⁴.

The most frequently observed of these translocations is the t(4;11) translocation involving the MLL gene and the AFF1 (AF4) gene on chromosome 4.^5,6 A 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 the 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 AFF1, MLLT3 and FEN1P1 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.

References:

1. Rubnitz et al., Blood 1994;84(2):570-3
2. Secker-Walker et al., Leukaemia 1998;12(5):840-4
3. Rowley, Annu Rev Genet 1998;32:495-519
4. Pui and Evans, New Engl J Med 1998;339(9):605-15
5. Felix and Lange, Oncologist 1999;4(3):225-40
6. Heerema et al., Leukemia 1999;13(5):679-86