Molecular analysis of t(X;11)(q24;q23) in an infant with AML-M4

t(X;11)(q24;q23) is a recurring chromosomal translocation in pediatric acute myeloid leukemia. The rearrangement results in fusion of MLL at 11q23 with SEPT6 at Xq24. Here, we report the identification of an MLL-SEPT6 fusion transcript in an infant with acute myeloid leukemia (AML)-M4. Reverse transcription-polymerase chain reaction confirmed the presence of an MLL-SEPT6 fusion transcript composed of exon 8 of MLL and exon 2 of SEPT6, but the absence of the reciprocal SEPT6-MLL fusion transcript. Sequence analysis of the genomic break junctions in MLL and SEPT6 suggested that the rearrangement in this case was the result of an insertion of the inverted Xq24 segment, which contained the 3′ region of SEPT6 intron I and up to 950 kb centromeric to SEPT6, into MLL intron 8. This is a novel type of chromosomal rearrangement leading to the MLL-SEPT6 fusion. The presence of deletions, duplications, and non-template DNA sequence at the break junctions suggested that the DNA damage-repair machinery is likely to be involved in the translocation events.