Identification of novel RUNXI (AMLI) translocation partner genes SH3D19, YTHDF2, and ZNF687 in acute myeloid leukemia
Identification of novel RUNXI (AMLI) translocation partner genes SH3D19, YTHDF2, and ZNF687 in acute myeloid leukemia
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DOI：
10.1002/gcc.20355
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发表时间：
2006-10-01
影响因子：
3.7
通讯作者：
Arber, Daniel A.
中科院分区：
文献类型：
--
作者：
Nguyen, TuDung T.;Ma, Lisa N.;Arber, Daniel A.
研究了3例诊断为急性髓性白血病（AML）的患者，这些患者伴有涉及染色体I和4的21 q22/RUNX 1（AML 1）相互易位。采用聚合酶链反应（PCR）和3'端快速扩增cDNA末端的方法，在1q21.2（ZNF 687）、1 p35（YTHDF 2）和4q31.3（SH 3D 19）上发现了3个新的RUNX 1易位伴侣基因。易位事件发生在RUNX 1基因的外显子3和7之间。伴侣基因断裂点位于伴侣基因中Alu密度最高的区域，表明Alus可能有助于重组事件。三分之二的病例在易位中保留了RUNX 1的整个RUNT结构域，并且通过逆转录聚合酶链反应和测序分析证实，融合转录本中不存在RUNX 1突变。SH 3D 19编码一种胞质蛋白EBP，已知其抑制RAS诱导的细胞转化，这种转化可被核募集抑制。t（4; 21）产生了保留RUNX 1的DNA结合结构域的杂合RUNX 1-EBP蛋白，这可能导致嵌合蛋白的核定位和抑制EBP的RAS抑制功能。未来的研究将有助于进一步表征这些新的融合蛋白产物。(c)2006 Wiley-Liss，Inc.
Three patients diagnosed with acute myeloid leukemia (AML) with reciprocal 21q22/RUNX1(AML1) translocations involving chromosomes I and 4 were studied. Three novel RUNX1 translocation partner genes on 1q21.2 (ZNF687), 1p35 (YTHDF2), and 4q31.3 (SH3D19) were identified using a panhandle polymerase chain reaction and the 3' rapid amplification of cDNA ends method. The translocation events occurred between exons 3 and 7 of the RUNX1 gene. The partner gene breakpoints localized to the region in the partner gene with the highest Alu density, suggesting that Alus may contribute to the recombination events. Two out of three of the cases retained RUNX1's entire RUNT domain in the translocation, and RUNX1 mutations were absent in the fusion transcripts, confirmed by reverse transcription-polymerase chain reaction and sequencing analysis. SH3D19 encodes a cytoplasmic protein EBP known to suppress RAS-induced cellular transformation, which can be inhibited by nuclear recruitment. The t(4;2 1) created a hybrid RUNX1-EBP protein retaining RUNX1's DNA binding domain, which may result in nuclear localization of the chimeric protein and inhibition of EBP's RAS-suppressive functions. Future studies would be useful to further characterize these novel fusion protein products. (c) 2006 Wiley-Liss, Inc.