title: MLL self fusion mediated by Alu repeat homologous recombination and prognosis of AML-M4/M5 subtypes.
abstract: Fifty-six patients with de novo acute myeloid leukemia M4/M5 subtypes were studied for rearrangements of the mixed lineage leukemia gene, MLL (also called HRX, Htrx-1, or ALL-1). Ten patients (18%) showed rearrangements of the MLL gene, 9 in a major breakpoint cluster region within a centromeric 8.3-kb BamHI fragment, whereas rearrangement in one patient was the result of a direct tandem duplication of exons 2-6 of MLL. Analysis of sequences at the duplication junction revealed that the points of MLL fusion within introns 6 and 1 both lie within Alu elements. This suggests the involvement of Alu repeat mediated homologous recombination in MLL self fusion. For the 10 rearranged samples, cytogenetics analysis revealed a normal karyotype in 3, and 3 had abnormalities other than 11q23. Survival analysis of patients revealed no difference between those with rearrangement of MLL and those showing the germ-line configuration.
authors.affiliation: Department of Pathology, University of Hong Kong, China.
authors.forename: C W
authors.initials: CW
authors.lastname: So
authors.forename: Z G
authors.initials: ZG
authors.lastname: Ma
authors.forename: C M
authors.initials: CM
authors.lastname: Price
authors.forename: S
authors.initials: S
authors.lastname: Dong
authors.forename: S J
authors.initials: SJ
authors.lastname: Chen
authors.forename: L J
authors.initials: LJ
authors.lastname: Gu
authors.forename: C K
authors.initials: CK
authors.lastname: So
authors.forename: L M
authors.initials: LM
authors.lastname: Wiedemann
authors.forename: L C
authors.initials: LC
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D007948:Leukemia, Monocytic, Acute / Q000235:genetics*; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis