MLL self fusion mediated by Alu repeat homologous recombination and prognosis of AML-M4/M5 subtypes
So, C.W.; Ma, Z.G.; Price, C.M.; Dong, S.; Chen, S.J.; Gu, L.J.; So, C.K.; Wiedemann, L.M.; Chan, L.C.
Cancer Research 57(1): 117-122
1997
ISSN/ISBN: 0008-5472 PMID: 8988051 Document Number: 474309
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.