MLL GENOMIC BREAKPOINT DISTRIBUTION WITHIN THE BREAKPOINT CLUSTER REGION IN DE-NOVO LEUKEMIA IN CHILDREN

Purpose: To assess translocation breakpoint distribution within the ML L genomic breakpoint cluster region (bcr), 40 cases of de novo leukemi a in children were examined by karyotype and Southern blot analysis. P atients and Methods: Criteria for inclusion were karyotypic or molecul ar rearrangement of chromosome band 11q23. Of the 40 cases, 31 occurre d in infants. Twenty cases were acute lymphoblastic leukemia (ALL), 17 were acute myeloid leukemia (AML), and 3 were biphenotypic. Results: Karyotype identified 27 cases with translocation of chromosome band 11 q23 and 2 with abnormalities of band 11q13 but not 11q23. Southern blo t analysis showed rearrangement within the MLL genomic bcr in 38 of th e 40 cases. In these 38, additional probe-restriction digest combinati ons localized MLL genomic breakpoints to the 5' portion of the bcr in 14 cases and to the 3' portion in 18; material was insufficient for fu rther localization to 5' or 3' within the bcr in 6 cases. In the two r emaining cases, both with t(4;11)(q21;q23), one breakpoint mapped 5' o f the bcr between intron 3 and exon 5, whereas the other breakpoint wa s neither within nor 5' of the MLL genomic bcr. Conclusions: Suggested trends warranting investigation in more patients were breakpoint site s in the 3' bcr in AML and in patients older than 12 months. The distr ibution of MLL genomic break points within the bcr in de novo leukemia in children is distinct from that in adults, where the breakpoints cl uster in the 5' portion of the bcr.