Molecular analysis of the rearranged genome and chimeric mRNAs caused by the t(6;11)(q27;q23) chromosome translocation involving MLL in an infant acute monocytic leukemia

Chromosomal analysis of acute monocytic leukemia cells in a female infant revealed a t(6;11)(q27;q23) translocation. Southern blot analysis with a cDNA probe of the MLL gene at chromosome band 11q23 indicated that the breakpoint was in an 8.3-kb BamHI fragment that contained exons 5-11 of the MLL gene. Northern blot analysis showed a faint band corresponding to the MLL chimeric transcript. Structural analysis of a genomic clone with the rearranged MLL gene from der(11) chromosome demonstrated the breakpoint to be localized between exons 6 and 7 of the the MLL gene and to lie in an Alu sequence of this region. The partner gene fused to the 3' part of MLL was shown to be the AF6 gene on chromosome 6q27 by in situ chromosome hybridization and nucleotide sequencing of chimeric MLL cDNA clones. However, it was shown that MLL exon 5 was fused to AF6 in one clone, whereas most clones were MLL exon 6/AF6 chimeric cDNA clones. These findings indicate that exon 6 of MLL is spliced out in the process of transcription in a variant MLL/AF6. In addition, we were able to detect the splicing of exon 6 in either this chimeric MLL/AF6 or MLL transcripts from untranslocated chromosomes by reverse transcriptase-polymerase chain reaction. The detailed genetic map of AF6 was determined by in situ chromosome hybridization and radiation hybrid mapping. (C) 2000 Wiley-Liss, Inc.