title: Identical fusion transcript associated with different breakpoints in the AML1 gene in simple and variant t(8;21) acute myeloid leukemia.
abstract: Fluorescence in situ hybridization (FISH) and/or RNA-based polymerase chain reaction (RT-PCR) were used to analyze the breakpoints within the AML1 gene and the AML1 fusion transcripts in t(8;21) acute myeloid leukemia (AML). Twenty-two patients presented with the simple t(8;21)(q22;q22) and one with a complex variant t(8;2;16;21). In eight cases we used FISH with AML1 cosmid probes on metaphase chromosomes as well as RT-PCR to detect the junctions of MAL1/CDR (ETO,MTG8). Five cases were analyzed by FISH alone and ten cases by RT-PCR alone. By FISH we could identify three groups according to the distribution of the fluorescent signal. Signals were found in group 1 on chromosomes 21 and 21q+, in group 2 on chromosomes 21, 21q+ and 8q- and in group 3 on chromosomes 21 and 8q-. In all groups we could detect an identical AML1/CDR fusion transcript. This transcript showed splicing of AML1 exon 5 onto CDR. Thus regardless of the heterogeneity suggested by FISH, all the breakpoints in the AML1 gene were clustered in the same intro between exons 5 and 6. Our results bring to over one hundred the number of t(8;21) cases in which an identical translocation could be detected at molecular level by RT-PCR. The high sensitivity of the technique makes it suitable for the diagnosis of this translocation in different stages of the disease. The impact of the molecular detection of t(8;21) cells in clinical remission as far as the treatment and the management of the disease are concerned deserves further discussion.
authors.affiliation: Department of Hematology, Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: G E
authors.initials: GE
authors.lastname: de Greef
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: R
authors.initials: R
authors.lastname: Morgan
authors.forename: J
authors.initials: J
authors.lastname: Wijsman
authors.forename: L H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: A A
authors.initials: AA
authors.lastname: Sandberg
authors.forename: N
authors.initials: N
authors.lastname: Sacchi
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001752:Blast Crisis / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16 / Q000648:ultrastructure; D002889:Chromosomes, Human, Pair 2 / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000648:ultrastructure*; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure*; D015331:Cohort Studies; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D014157:Transcription Factors