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Incidence and characterization of MLL gene (11q23) rearrangements in acute
myeloid leukemia M1 and M5
H Poirel, K Rack, E Delabesse, I Radford-Weiss, X Troussard, C Debert, D Leboeuf, C Bastard, F Picard, A Veil-Buzyn, G Flandrin, O Bernard and E Macintyre
Department of Haematology, University Paris V, France.
To determine the incidence of MLL rearrangement in acute myeloid leukemia
(AML) French-American-British (FAB) type M1 and to evaluate optimal
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
transcription-polymerase chain reaction (RT-PCR) and fluorescent in situ
hybridization (FISH) to identify the types of rearrangement found in AML 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 of 11 cases showed
four MLL self- fusions, four MLL-AF6, two MLL-AF9, including a novel AF9
breakpoint, and one uncharacterized t(11:19). Only 5 of 10 MLL-rearranged
cases tested demonstrated karyotypic 11q23 abnormalities. FISH analysis of
nine cases with an MLL-specific yeast artificial chromosome (YAC) confirmed
the cytogenetic abnormalities in two cases, clarified them in one, and did
not detect six cases, including three MLL self-fusions, one case with a
probable MLL-rearranged subclone not represented karyotypically, and
twoMLL-AF6. A whole chromosome 11 paint detected one of these MLL-AF6, and
an AF6 cosmid demonstrated that the other was probably due to insertion of
a submicroscopic portion of chromosome 6, including part of AF6, into an
apparently normal chromosome 11. We conclude that MLL rearrangements are
common in adult AML M1, that MLL self-fusion and MLL-AF6 are the most
frequent types of abnormalities, and that RT-PCR is preferable to 11q23
FISH analysis for their characterization.
Volume 87,
Issue 6,
pp. 2496-2505,
03/15/1996
Copyright © 1996 by The American Society of Hematology

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