The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin retinoic acid receptor fusion
The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin retinoic acid receptor fusion
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DOI：
10.1182/blood.v87.3.882.bloodjournal873882
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发表时间：
1996-02-01
期刊：
影响因子：
20.3
通讯作者：
Corey, SJ
中科院分区：
文献类型：
--
作者：
Redner, RL;Rush, EA;Corey, SJ
我们研究了一个具有变异t(5;17)（q32;q12）的急性早幼粒细胞白血病（APL）患者，这种易位将核仁磷酸化蛋白核磷蛋白（NPM）基因融合到视黄酸受体α (RARA)上。NPM- rar cDNA短片段中包含的NPM序列与t（2;5）淋巴瘤中表达的NPM- alk融合基因中包含的NPM序列相同。RARA序列与t（15;17）和t(11;17) APL中PML-RAR和PLZF-RAR融合的RARA序列相同，NPM- rar转录本在同一阅读框中融合NPM和RARA序列，产生57kd和62kd的翻译产物。两种NPM-RAR蛋白都在患者的白血病细胞中表达，以及来自非相关等位基因的野生型RARA。在使用视黄酸反应元件报告构建的转录分析中，两种NPM-RAR融合蛋白都作为视黄酸依赖性转录激活因子。这种情况定义了第三类APL重排，它们都产生RARA的融合蛋白。(C) 1996年由美国血液病学会出版。
We have studied an acute promyelocytic leukemia (APL) patient with a variant t(5;17)(q32;q12), This translocation fuses the gene for the nucleolar phosphoprotein nucleophosmin (NPM) to the retinoic acid receptor alpha (RARA). Two alternatively spliced transcripts are expressed, which differ in 129 bases immediately upstream of the RARA sequence, The NPM sequences contained in the shorter NPM-RAR cDNA are identical to the NPM sequences contained in the NPM-ALK fusion gene expressed in t(2;5) lymphomas. The RARA sequences are the same as the RARA sequences found in the PML-RAR and PLZF-RAR fusion seen in t(15;17) and t(11;17) APL, respectively, Both NPM-RAR transcripts fuse NPM and RARA sequence in the same reading frame, to generate translation products of 57 kD and 62 kD. Both NPM-RAR proteins are expressed in the patient's leukemic cells, along with wild-type RARA derived from the uninvolved allele. In transcriptional assays using a retinoic acid response element reporter construct, both NPM-RAR fusion proteins act as retinoic acid-dependent transcriptional activators. This case defines a third class of APL rearrangements, all of which generate fusion proteins of RARA. (C) 1996 by The American Society of Hematology.