Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25)
Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25)
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DOI：
10.1182/blood.v93.4.1355
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发表时间：
1999-02-15
期刊：
影响因子：
20.3
通讯作者：
Kamada, N
中科院分区：
文献类型：
--
作者：
Eguchi, M;Eguchi-Ishimae, M;Kamada, N
已知涉及带12 p13的染色体易位涉及多种血液恶性肿瘤，其中一些导致ETV 6/TEL基因重排。应用荧光原位杂交（FISH）技术，在1例成人急性髓系白血病（AML）患者中发现了t（12;15）（p13;q25）的隐性易位。与粘粒探针的杂交表明ETV 6基因在这次易位中发生了重排。用ETV 6 cDNA筛选患者特异性cDNA文库，并鉴定了ETV 6与位于15 q25的TRKC/NTRK 3基因之间的新融合转录物。TRKC是由神经营养因子-3（NT-3）激活的受体酪氨酸激酶。目前已知它广泛表达于神经组织，但在血液细胞中不表达。ETV 6-TRKC嵌合转录物编码ETV 6基因的尖（PNT）结构域，其与TRKC基因的蛋白酪氨酸激酶（PTK）结构域融合。确定了两种类型的融合转录物，一种是包括TRKC的整个PTK结构域，另一种是TRKC的3 '末端462 bp在PTK结构域内被截短。Western blot分析表明，这两个嵌合蛋白的表达大小为52和38 kD。我们的研究结果表明，嵌合PTK在白血病细胞中表达可能有助于细胞转化异常激活TRK信号通路。此外，这是关于白血病相关的截短神经营养因子受体的首次报道。(C)1999年，美国血液学会。
Chromosome translocations involving band 12p13 are known to be involved in a variety of hematologic malignancies, some of them resulting in rearrangement of the ETV6/TEL gene. Applying the fluorescence in situ hybridization (FISH) method, we found a cryptic translocation t(12;15)(p13;q25) in an adult acute myeloid leukemia (AML) patient. Hybridization with cosmid probes showed that the ETV6 gene was rearranged in this translocation. A patient-specific cDNA library was screened with ETV6 cDNA, and a novel fusion transcript was identified between the ETV6 and TRKC/NTRK3 gene located on 15q25. TRKC is a receptor tyrosine kinase that is activated by neurotrophin-3 (NT-3). It is known to be expressed broadly in neural tissues but not in hematologic cells, so far. ETV6-TRKC chimeric transcript encoded the pointed (PNT) domain of the ETV6 gene that fused to the protein-tyrosine kinase (PTK) domain of the TRKC gene. Two types of fusion transcript were determined, one that included the entire PTK domain of TRKC and the other in which the 3'-terminal 462 bp of TRKC was truncated within the PTK domain. Western blot analysis showed the expression of both chimeric proteins of 52 and 38 kD in size. Our results suggest that chimeric PTK expressed in the leukemic cells may contribute to cellular transformation by abnormally activating TRK signaling pathways. Moreover, this is the first report on truncated neurotrophin receptors associated in leukemia. (C) 1999 by The American Society of Hematology.