title: Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.
abstract: 16;21 translocation is a recurrent primary abnormality in acute myeloid leukemia (AML). The genes involved in this translocation are ERG on chromosome 21 and TLS/FUS on chromosome 16. The rearrangement of the two chromosomes forms the TLS/FUS-ERG fusion gene and produces a consistent chimeric transcript on the der (21) chromosome. In this study, we analyzed the clinical characteristics of 19 patients with t(16;21)-AML, including 2 patients who evolved from myelodysplastic syndrome, and detected the chimeric transcripts of the TLS/FUS-ERG fusion gene in the patients during various clinical stages by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. We found that the patients with t(16;21) are characterized by a relatively younger age (median age, 22 years old), involvement of various subtypes of French-American-British classification and a poor prognosis: 18 of the 19 patients died of the disease (median survival was 16 months). Four types of TLS/FUS-ERG chimeric transcripts including a novel type were noted in the RT-PCR analysis. The novel transcript contained an additional 138 nucleotides consisting of TLS/FUS exon 8 and ERG exons 7 and 8 and had an in-frame fusion. These chimeric transcripts were consistently detectable in the samples obtained not only at diagnosis and relapse but also in short and long complete remission, suggesting that t(16;21)-AML is resistant to conventional chemotherapy. Thus, we recommend that t(16;21) should be monitored by RT-PCR even in clinical remission and the patients should be treated by other more powerful modality like stem-cell transplantation in the first remission.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Japan.
authors.forename: X T
authors.initials: XT
authors.lastname: Kong
authors.forename: K
authors.initials: K
authors.lastname: Ida
authors.forename: H
authors.initials: H
authors.lastname: Ichikawa
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.forename: M
authors.initials: M
authors.lastname: Ohki
authors.forename: N
authors.initials: N
authors.lastname: Maseki
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneko
authors.forename: M
authors.initials: M
authors.lastname: Sako
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: A
authors.initials: A
authors.lastname: Tojou
authors.forename: I
authors.initials: I
authors.lastname: Miura
authors.forename: H
authors.initials: H
authors.lastname: Kakuda
authors.forename: T
authors.initials: T
authors.lastname: Funabiki
authors.forename: K
authors.initials: K
authors.lastname: Horibe
authors.forename: H
authors.initials: H
authors.lastname: Hamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: F
authors.initials: F
authors.lastname: Bessho
authors.forename: M
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics* / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics* / Q000648:ultrastructure; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D034702:RNA-Binding Protein FUS; D012074:Remission Induction; D016019:Survival Analysis; D015534:Trans-Activators; D014157:Transcription Factors; D014158:Transcription, Genetic; D000071230:Transcriptional Regulator ERG; D014178:Translocation, Genetic; D017211:Treatment Failure
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034702:RNA-Binding Protein FUS; C107302:TLS-ERG fusion protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG