title: Incidence and characterization of MLL gene (11q23) rearrangements in acute myeloid leukemia M1 and M5.
abstract: 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.
authors.affiliation: Department of Haematology, University Paris V, France.
authors.forename: H
authors.initials: H
authors.lastname: Poirel
authors.forename: K
authors.initials: K
authors.lastname: Rack
authors.forename: E
authors.initials: E
authors.lastname: Delabesse
authors.forename: I
authors.initials: I
authors.lastname: Radford-Weiss
authors.forename: X
authors.initials: X
authors.lastname: Troussard
authors.forename: C
authors.initials: C
authors.lastname: Debert
authors.forename: D
authors.initials: D
authors.lastname: Leboeuf
authors.forename: C
authors.initials: C
authors.lastname: Bastard
authors.forename: F
authors.initials: F
authors.lastname: Picard
authors.forename: A
authors.initials: A
authors.lastname: Veil-Buzyn
authors.forename: G
authors.initials: G
authors.lastname: Flandrin
authors.forename: O
authors.initials: O
authors.lastname: Bernard
authors.forename: E
authors.initials: E
authors.lastname: Macintyre
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D018244:Chromosomes, Artificial, Yeast; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics* / Q000648:ultrastructure; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics*; D004314:Down Syndrome / Q000150:complications; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007948:Leukemia, Monocytic, Acute / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011519:Proto-Oncogenes; D012189:Retrospective Studies; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase