The tyrosine kinase Abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13):: Molecular cloning of both reciprocal transcripts
The tyrosine kinase Abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13):: Molecular cloning of both reciprocal transcripts
复制标题
DOI：
10.1182/blood.v94.12.4370.424k34_4370_4373
复制
发表时间：
1999-12-15
期刊：
影响因子：
20.3
通讯作者：
Biondi, A
中科院分区：
文献类型：
--
作者：
Cazzaniga, G;Tosi, S;Biondi, A
大多数 12p13 易位患者的 Ets 变异基因 6 (ETV6/TEL) 基因会重新排列，与许多不同的伴侣融合。我们在这里介绍一例伴有嗜酸性粒细胞增多的急性髓系白血病 M4 (AML-M4Eo) 病例，其 CBFb/MYH11 重排呈阳性，并携带涉及 12p13 处 ETV6 基因的 t(1;12)(q25;p13)。通过 cDNA 末端聚合酶链式反应 (3'RACE-PCR) 的 3' 快速扩增，在 ETV6 和 Abelson 相关基因 (ARG) 1q25 之间鉴定出一种新的融合转录物，产生由 ETV6 的 HLH 寡聚结构域和 ARG 的 SH2、SH3 和蛋白酪氨酸激酶 (PTK) 结构域组成的嵌合蛋白。通过逆转录酶-聚合酶链式反应 (RT-PCR) 在患者 RNA 中也检测到了互逆转录物 ARG-ETV6，尽管表达水平较低。 ARG 基因编码非受体酪氨酸激酶，其特征在于 TK、SH2 和 SH3 结构域中与 c-Abl 高度同源。这是第一份关于 ARG 参与人类恶性肿瘤的报告。 (C) 1999 年，美国血液学会。
The Ets variant gene 6 (ETV6/TEL) gene is rearranged in the majority of patients with 12p13 translocations fused to a number of different partners. We present here a case of acute myeloid leukemia M4 with eosinophilia (AML-M4Eo) positive for the CBFb/MYH11 rearrangement and carrying a t(1;12)(q25;p13) that involves the ETV6 gene at 12p13. By 3' rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG. The reciprocal transcript ARG-ETV6 was also detected in the patient RNA by reverse transcriptase-polymerase chain reaction (RT-PCR), although at a lower expression level. The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains. This is the first report on ARG involvement in a human malignancy. (C) 1999 by The American Society of Hematology.