MLL translocations with concurrent 3′ deletions: Interpretation of FISH results

Rearrangements involving the MLL gene at 11q23 occur in a clinically relevant subgroup of patients with acute lymphoblastic leukemia (ALL) at all ages, and therefore their accurate identification at diagnosis is important. It has become commonplace to screen ALL patients for rearrangements of MLL using a dual-color fluorescence in situ hybridization (FISH) assay. We report on 12 ALL patients with an unusual FISH result consisting of the following signal pattern: one 5′ green, no 3′ red, and one/two fusion signals. This configuration is consistent with a MLL translocation and simultaneous deletion of 3′ MLL-a well-established phenomenon-which has been interpreted as a positive result. G-banded and complementary metaphase FISH analyses confirmed an 11q23/MLL translocation in 8 of the 12 cases, whereas in one case, the identification of a del(11)(q23) was restricted to G-banded analysis only. In three cases, an MLL rearrangement was excluded by extensive FISH analysis and/or Southern blotting. In conclusion, the loss of the 3′ MLL signal should not be assumed to be the result of a concurrent translocation and deletion event, and such aberrant FISH signal patterns should be investigated further by alternative methods for determining their MLL status.