Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia
Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia
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DOI：
10.1182/blood.v90.7.2535.2535_2535_2540
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发表时间：
1997-10-01
期刊：
影响因子：
20.3
通讯作者：
Marynen, P
中科院分区：
文献类型：
--
作者：
Peeters, P;Raynaud, SD;Marynen, P
在染色体带12 p13处具有断裂点的骨髓或淋巴起源的血液病中的易位经常导致Ets变体基因6（ETV 6）的重排。因此，ETV 6的ETS DNA结合结构域或螺旋环抑制（HLH）寡聚化结构域与不同的配偶体基因融合。我们在这里显示，在早期前B急性淋巴细胞白血病的情况下，t（9;12）（p24;p13）和t（9;15;12）（p24;q15;p13）在转化的非典型慢性髓细胞白血病涉及ETV 6基因在12 p13和JAK 2基因在9 p24。在每种情况下，发现了不同的融合mRNA，其中只有一种导致由ETV 6的HLH寡聚化结构域和JAK 2的蛋白酪氨酸激酶（PTK）结构域组成的嵌合蛋白的开放阅读框。完整的人JAK 2编码和基因组序列以及易位的基因组连接片段的克隆允许表征导致各种mRNA的不同剪接事件。JAK 2在非蛋白酪氨酸激酶受体信号通路中起着核心作用，这可以解释其参与不同血液谱系的恶性肿瘤。除了果蝇中的啤酒花，JAK家族中还没有任何成员与肿瘤发生有关。(C)1997年，美国血液学会。
Translocations in hematologic disease of myeloid or lymphoid origin with breakpoints at chromosome band 12p13 frequently result in rearrangements of the Ets variant gene 6 (ETV6). As a consequence either the ETS DNA-binding domain or the Helix-Loop-Helix (HLH) oligomerization domain of ETV6 is fused to different partner genes. We show here that a t(9;12)(p24;p13) in a case of early pre-B acute lymphoid leukemia and a t(9;15;12)(p24;q15;p13) in atypical chronic myelogenous leukemia in transformation involve the ETV6 gene at 12p13 and the JAK2 gene at 9p24. In each case different fusion mRNAs were found, with only one resulting in an open reading frame for a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the protein tyrosine kinase (PTK) domain of JAK2. The cloning of the complete human JAK2 coding and genomic sequences and of the genomic junction fragments of the translocations allowed a characterization of the different splice events leading to the various mRNAs. JAK2 plays a central role in non-protein tyrosine kinase receptor signaling pathways, which could explain its involvement in malignancies of different hematologic lineages. Besides hop in Drosophila no member of the JAK family has yet been implicated in tumorigenesis. (C) 1997 by The American Society of Hematology.