MLL ENL FUSION IN CONGENITAL ACUTE LYMPHOBLASTIC-LEUKEMIA WITH A UNIQUE T(11-18-19)/

To elucidate the events leading to a unique complex translocation invo lving chromosomes 11, 18, and 19 in a congenital progenitor B-cell acu te lymphoblastic leukemia, we have performed comprehensive cytogenetic and fluorescence in situ hybridization (FISH) analyses as well as mol ecular genetic studies on the DNA and RNA level. We were able to confi rm the cytogenetic interpretation of this complex t(11;18;19)(q23;q22; p13.3) by chromosome painting. Involvement of the MLL gene on 11q23 be came evident by Southern blot analysis as well as by FISH with a YAC c lone containing the respective gene. Despite the fact that the additio nal signals of the split YAC clone were observed on the abnormal chrom osome 18, reverse transcription polymerase chain reaction (RT-PCR) rev ealed 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 thi s rearrangement. The transfer of the translocated part of the split YA C clone onto chromosome 18 indicates that the second break must have o ccurred in the vicinity of the first one, at a distance too close to b e 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 m aterial or from two separate sequential events in consecutive cell gen erations remains open.