title: A multicenter evaluation of comprehensive analysis of MLL translocations and fusion gene partners in acute leukemia using the MLL FusionChip device.
abstract: Rearrangements of the MLL gene are significant in acute leukemia. Among the most frequent translocations are t(4;11)(q21;q23) and t(9;11)(p22;q23), which give rise to the MLL-AFF1 and MLL-MLLT3 fusion genes (alias MLL-AF4 and MLL-AF9) in acute lymphoblastic and acute myeloid leukemia, respectively. Current evidence suggests that determining the MLL status of acute leukemia, including precise identification of the partner gene, is important in defining appropriate treatment. This underscores the need for accurate detection methods. A novel molecular diagnostic device, the MLL FusionChip, has been successfully used to identify MLL fusion gene translocations in acute leukemia, including the precise breakpoint location. This study evaluated the performance of the MLL FusionChip within a routine clinical environment, comprising nine centers worldwide, in the analysis of 21 control and 136 patient samples. It was shown that the assay allowed accurate detection of the MLL fusion gene, regardless of the breakpoint location, and confirmed that this multiplex approach was robust in a global multicenter trial. The MLL FusionChip was shown to be superior to other detection methods. The type of molecular information provided by MLL FusionChip gave an indication of the appropriate primers to design for disease monitoring of MLL patients following treatment.
authors.affiliation: Leukaemia Research Cytogenetics Group, Cancer Sciences Division, University of Southampton, MP 822 Duthie Building, Southampton General Hospital, Southampton SO16 6YD, UK. harrison@soton.ac.uk
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: Mike
authors.initials: M
authors.lastname: Griffiths
authors.forename: Fìona
authors.initials: F
authors.lastname: Moorman
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Sheila
authors.initials: S
authors.lastname: Shurtleff
authors.forename: Enrico
authors.initials: E
authors.lastname: Gottardi
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Mitterbauer
authors.forename: Dolores
authors.initials: D
authors.lastname: Colomer
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Vincent
authors.initials: V
authors.lastname: Castéras
authors.forename: Nicolas
authors.initials: N
authors.lastname: Maroc
mesh_terms: D000208:Acute Disease; D000328:Adult; D002648:Child; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D002899:Chromosomes, Human, Pair 9; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation / Q000379:methods; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: C497422:KMT2A protein, human; C113855:MLL-AF4 fusion protein, human; C474558:MLL-AF9 fusion protein, human; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase