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Breakpoint Heterogeneity in t(10;11) Translocation in AML-M4/M5 Resulting in Fusion of AF10 and MLL Is Resolved by Fluorescent in Situ Hybridization Analysis¹

Erasmus University, Department of Cell Biology and Genetics, P. O. Box 1738, 3000 DR Rotterdam, the Netherlands [H. B. B., J. W., A. d. K., A. H.]; Unite INSERM U 301, Institut de Genetique Moleculaire, 27 Rue Juliette Dodu, 75010 Paris, France [M. L. C., O. B., R. B.]; Imperial Cancer Research Fund, Department of Medical Oncology, St. Bartholomew's Hospital Medical College, London EC1M 6BQ, United Kingdom [D. M. L., B. D. Y.]; Dutch Childhood Leukemia Study Group, Leyweg 299, 2545 CJ The Hague, the Netherlands [E. v. W.]; and University of California, University of California Davis Medical Center, Hematology and Oncology, Sacramento, California 95816 [J. W.]

Ten AML-M4/M5 patients' samples containing a t(10;11) translocation, but with different cytogenetic breakpoints on chromosome 11q (11q13–23), were studied by G- and R-banding and fluorescent in situ hybridization. Southern blotting analysis, studied in five patients, revealed a rearranged MLL gene. Reverse transcription-PCR analysis carried out in six patients showed a 5' MLL-3' AF-10 fusion transcript. Fluorescent in situ hybridization studies suggested that in 8 of 10 patients, the rearrangement/fusion transcript resulted from an inversion of a part of 11q (q13q23) translocated to 10p12. In the other two patients, it is assumed that an inversion/translocation has occurred of a part of 10p to the der(11).

The results suggest that the orientation of the AF-10 gene on 10p is 5' telomeric and 3' centromeric. This is the first example of opposite-oriented genes being involved in translocation to yield fusion transcripts.

¹ This study was supported by European Union Grant CT93-0055 (B. B.), European Union Grant CA CT94-1703 (A. H., B. D. Y., R. B.), by the Fondation contre la Leucemie, and by the Caroline Lawson Trust for Children's Cancer Research.

² To whom requests for reprints should be addressed.

Received 7/11/95. Accepted 8/18/95.

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