Kong X T, Ida K, Ichikawa H, Shimizu K, Ohki M, Maseki N, Kaneko Y, Sako M, Kobayashi Y, Tojou A, Miura I, Kakuda H, Funabiki T, Horibe K, Hamaguchi H, Akiyama Y, Bessho F, Yanagisawa M, Hayashi Y
Department of Pediatrics, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Japan.
Blood. 1997 Aug 1;90(3):1192-9.
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.
16;21易位是急性髓系白血病（AML）中一种常见的原发性异常。参与这种易位的基因是21号染色体上的ERG和16号染色体上的TLS/FUS。两条染色体的重排形成了TLS/FUS-ERG融合基因，并在der(21)染色体上产生一致的嵌合转录本。在本研究中，我们分析了19例t(16;21)-AML患者的临床特征，其中包括2例由骨髓增生异常综合征演变而来的患者，并通过逆转录聚合酶链反应（RT-PCR）技术检测了患者在不同临床阶段的TLS/FUS-ERG融合基因的嵌合转录本。我们发现，t(16;21)患者的特点是年龄相对较小（中位年龄22岁），涉及法美英分类的各种亚型，预后较差：19例患者中有18例死于该病（中位生存期为16个月）。RT-PCR分析中发现了四种类型的TLS/FUS-ERG嵌合转录本，包括一种新型转录本。这种新型转录本包含另外138个核苷酸，由TLS/FUS外显子8和ERG外显子7和8组成，并且具有读框内融合。这些嵌合转录本不仅在诊断和复发时，而且在短期和长期完全缓解期获得的样本中都能持续检测到，这表明t(16;21)-AML对传统化疗耐药。因此，我们建议即使在临床缓解期也应通过RT-PCR监测t(16;21)，并且患者应在首次缓解期接受其他更有效的治疗方式，如干细胞移植。
