INCIDENCE AND CHARACTERIZATION OF MLL GENE (11Q23) REARRANGEMENTS IN ACUTE MYELOID-LEUKEMIA M1 AND M5

To determine the incidence of MLL rearrangement in acute myeloid leuke mia (AML) French-American-British (FAB) type M1 and to evaluate optima l screening strategies for the characterization of such abnormalities, we analyzed specimens from 41 patients with AML by Southern blotting with two MLL genomic probes and compared the capacities of reverse tra nscription-polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH) to identify the types of rearrangement found in A ML M1 with those observed in AML M5. MLL rearrangement was found in 6 of 29 (20%) AML M1 and 6 of 10 AML M5 cases. RT-PCR characterization o f 11 cases showed four MLL self-fusions, four MLL-AF6, two MLL-AF9, in cluding a novel AF9 breakpoint, and one uncharacterized t(11;19). Only 5 of 10 MLL-rearranged cases tested demonstrated karyotypic 11q23 abn ormalities. FISH analysis of nine cases with an MLL-specific yeast art ificial chromosome (YAC) confirmed the cytogenetic abnormalities in tw o cases, clarified them in one, and did not detect six cases, includin g three MLL self-fusions, one case with a probable MLL-rearranged subc lone not represented karyotypically, and two MLL-AF6. A whole chromoso me 11 paint detected one of these MLL-AF6, and an AF6 cosmid demonstra ted that the other was probably due to insertion of a submicroscopic p ortion of chromosome 6, including part of AF6, into an apparently norm al chromosome 11. We conclude that MLL rearrangements are common in ad ult AML M1, that MLL self-fusion and MLL-AF6 are the most frequent typ es of abnormalities, and that RT-PCR is preferable to 11q23 FISH analy sis for their characterization. (C) 1996 by The American Society of He matology.