Cryptic t(4;11) encoding MLL-AF4 due to insertion of 5 ' MLL sequences in chromosome 4

The t(4;11) translocation is the cytogenetic hallmark of a subset of acute lymphoblastic leukemias characterized by pro-B immunophenotype and a dismal prognosis. This translocation fuses the MLL gene on chromosome band 11q23 and the AF4 gene on 4q21, resulting in the expression of fusion transcripts from both translocated chromosomes. The MLL-AF4 chimeric transcript is tho ught to mediate the leukemic transformation. The MLL genomic disruption det ected by Southern blot and the RT-PCR for the MLL-AF4 chimeric transcript e xpression are molecular evidence of this chromosomal translocation. However , similar molecular rearrangements have also been identified in cases witho ut the cytogenetic t(4;11). We report a 30-year-old patient with high risk ALL, a normal karyotype, and molecular evidence of MLL-AF4 fusion, Using a double color FISH assay with MLL specific PAC probes, a cryptic t(4;11) due to insertion of 5' MLL sequences in chromosome 4q21 was demonstrated. Cons equently the MLL-AF4 was encoded by der(4). This insertion mechanism preclu des the genomic recombination of AF4-MLL end supports the crucial role play ed by MLL-AF4 in leukemogenesis. The findings of our case, along with other s, show the importance of complementing the karyotype with molecular and FI SH techniques.