To elucidate the events leading to a unique complex translocation involving chromosomes 11, 18, and 19 in a congenital progenitor B-cell acute lymphoblastic leukemia, we have performed comprehensive cytogenetic and fluorescence in situ hybridization (FISH) analyses as well as molecular genetic studies on the DNA and RNA level. We were able to confirm the cytogenetic interpretation of this complex t(11;18;19)(q23;q22;p13.3) by chromosome painting. Involvement of the MLL gene on 11q23 became evident by Southern blot analysis as well as by FISH with a YAC clone containing the respective gene. Despite the fact that the additional signals of the split YAC clone were observed on the abnormal chromosome 18, reverse transcription polymerase chain reaction (RT-PCR) revealed a MLL/ENL hybrid mRNA, which is specific for a t(11;19)(q23;p13.3). This gene fusion most probably represents the critical part of this rearrangement. The transfer of the translocated part of the split YAC clone onto chromosome 18 indicates that the second break must have occurred in the vicinity of the first one, at a distance too close to be resolved by FISH. Whether this break took place within chromosome 11 or 19 sequences, up- or downstream of the MLL/ENL fusion, and whether this translocation results from a concerted simultaneous exchange of material or from two separate sequential events in consecutive cell generations remains open.
