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Consistent Detection of TLS/FUS-ERG Chimeric Transcripts in Acute Myeloid Leukemia With t(16; 21)(p11; q22) and Identification of a Novel Transcript
Xiao-Tang Kong,
Kohmei Ida,
Hitoshi Ichikawa,
Kimiko Shimizu,
Misao Ohki,
Nobuo Maseki,
Yasuhiko Kaneko,
Masahiro Sako,
Yukio Kobayashi,
Arinobu Tojou,
Ikuo Miura,
Harumi Kakuda,
Tetsunori Funabiki,
Keizo Horibe,
Hiroyuki Hamaguchi,
Yuichi Akiyama,
Fumio Bessho,
Masayoshi Yanagisawa, and
Yasuhide Hayashi
From the Department of Pediatrics, Faculty of Medicine, University of Tokyo; National Cancer Center Research Institute, Tokyo; Hematology Clinic, Saitama Cancer Center, Saitama; the Department of Pediatrics, Osaka City General Hospital; Institute of Medical Science, University of Tokyo; Third Department of Internal Medicine, Akita University School of Medicine; the Department of Pediatrics, School of Medicine, Chiba University; the Department of Pediatrics, Yokohama City University School of Medicine; the Department of Pediatrics, Nagoya University School of Medicine; the Department of Hematology, Musashino Red Cross Hospital, Tokyo; the Department of Pediatrics, Graduate School of Medicine, Kyoto University, Japan.
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.
Blood, Vol. 90 No. 3 (August 1), 1997:
pp. 1192-1199
© 1997 by The American Society of Hematology.
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