NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia.
NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia.
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发表时间：
1998-10
期刊：
影响因子：
11.2
通讯作者：
S. Z. Raza-Egilmez;S. Jani-Sait;M. Grossi;M. Higgins;T. Shows;P. Aplan
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文献类型：
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作者：
S. Z. Raza-Egilmez;S. Jani-Sait;M. Grossi;M. Higgins;T. Shows;P. Aplan
在患有与治疗相关的急性急性骨髓性白血病（T-AML）的患者中发现了一种新型的染色体易位T（2; 11）（Q31; p15）。荧光原位杂交实验映射了NUP98附近的断点。 Southern印迹分析表明，核孔基因NUP98被这种易位破坏了。我们使用cDNA末端的快速扩增来鉴定嵌合mRNA。将NUP98序列融合到同型基因HOXD13的框内嵌合mRNA。预测的融合蛋白既包含NUP98的GLFG重复序列，也包含来自HOXD13的同源域。 NUP98-HOXD13融合在结构上与以前在AML患者中鉴定的NUP98-HOXA9融合相似，导致人们猜测NUP98-Homeobox基因融合可能是致癌的。此外，这份报告以及最近的一项研究表明，T-AML患者的NUP98-DDX10融合，提高了NUP98可能是先前未经偶然的T-AML染色体易位靶标。
A novel chromosomal translocation, t(2;11)(q31;p15), was identified in a patient with therapy-related acute myelogenous leukemia (t-AML). Fluorescence in situ hybridization experiments mapped the breakpoint near NUP98; Southern blot analysis demonstrated that the nucleoporin gene NUP98 was disrupted by this translocation. We used rapid amplification of cDNA ends to identify a chimeric mRNA. An in-frame, chimeric mRNA that fused NUP98 sequences to the homeobox gene HOXD13 was cloned; the predicted fusion protein contains both the GLFG repeats from NUP98 as well as the homeodomain from HOXD13. The NUP98-HOXD13 fusion is structurally similar to the NUP98-HOXA9 fusion previously identified in patients with AML, leading to the speculation that NUP98-homeobox gene fusions may be oncogenic. Moreover, this report, along with a recent study that demonstrated NUP98-DDX10 fusions in patients with t-AML, raises the possibility that NUP98 may be a previously unsuspected target for chromosomal translocations in patients with t-AML.