A multicenter evaluation of comprehensive analysis of MLL translocations and fusion gene partners in acute leukemia using the MLL FusionChip device.
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.
Harrison
Christine J
CJ
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
Griffiths
Mike
M
Moorman
Fìona
F
Schnittger
Susanne
S
Cayuela
Jean-Michel
JM
Shurtleff
Sheila
S
Gottardi
Enrico
E
Mitterbauer
Gerlinde
G
Colomer
Dolores
D
Delabesse
Eric
E
Castéras
Vincent
V
Maroc
Nicolas
N
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
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