A novel MLL/AF4 fusion gene lacking the AF4 transactivating domain in infant acute lymphoblastic leukemia.

Southern anal. of the MLL Locus in DNA from bone marrow cells samples from a 5-mo old child with acute lymphoblastic leukemiasampled at diagnosis revealed a rearrangement at locus MLL of chromosome 11q23. Panhandle PCR amplification of the fragment comprising the der(11) translocation breakpoints yielded a 4.6 kb fragment corresponding to the bamHI-rearranged fragment detected by Southern anal. The new fusion gene lacks both the AF4-derived and the MLL-derived (nucleotide 2772-3579) transactivating domain. The resulting fusion protein is able to bind DNA through the MLL-derived AT hook domain, and through the AF4-derived nuclear targeting sequence domain but could lose its capacity to activate the expression of these genes.