BREAKPOINT HETEROGENEITY IN T(10-11) TRANSLOCATION IN AML-M4 M5 RESULTING IN FUSION OF AF1O AND MLL IS RESOLVED BY FLUORESCENT IN-SITU HYBRIDIZATION ANALYSIS/

Ten AML-M4/M5 patients' samples containing a t(10;11) translocation, b ut with different cytogenetic breakpoints on chromosome 11q (11q13-23) , were studied by G- and R-banding and fluorescent in situ hybridizati on. Southern blotting analysis, studied in five patients, revealed a r earranged MLL gene. Reverse transcription-PCR analysis carried out in six patients showed a 5' MLL-3' AF-10 fusion transcript. Fluorescent i n situ hybridization studies suggested that in 8 of 10 patients, the r earrangement/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-IO gene on 10p is 5' telomeric and 3' centromeric. This is the first exam ple of opposite-oriented genes being involved in translocation to yiel d fusion transcripts.