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Hematology Section, Department of Pathology, The University of Hong Kong, Hong Kong, Hong Kong [C. W. S., C. K. C. S., L. C. C.]; Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Second Medical University, Shanghai, China [Z. G. M., S. D., S. J. C.]; Leukemia Research Fund Centre, Institute of Cancer Research, London, United Kingdom [C. M. P., L. M. W.]; and Xin-Hua Hospital, Shanghai Second Medical University, Shanghai, China [L. J. G.]
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.
1 Supported by CRCG Grant 335/046/0060 (to L. C. C.). C. W. S. is a Ph.D. student of the University of Hong Kong and supported by a Croucher Foundation Scholarship.
2 To whom requests for reprints should be addressed, at Hematology Section, Department of Pathology, Queen Mary Hospital, Hong Kong, Hong Kong.
Received 9/16/96. Accepted 10/28/96.
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