Yoneda-Kato N, Look A T, Kirstein M N, Valentine M B, Raimondi S C, Cohen K J, Carroll A J, Morris S W
Department of Experimental Oncology, St. Jude Children's Research Hospital.
Oncogene. 1996 Jan 18;12(2):265-75.
A t(3;5)(q25.1;q34) chromosomal translocation associated with myelodysplastic syndrome and acute myeloid leukemia (AML) was found to rearrange part of the nucleophosmin (NPM) gene on chromosome 5 with sequences from a novel gene on chromosome 3. Chimeric transcripts expressed by these cells contain 5' NPM coding sequences fused in-frame to those of the new gene, which we named myelodysplasia/myeloid leukemia factor 1 (MLF1). RNA-based polymerase chain reaction analysis revealed identical NPM-MLF1 mRNA fusions in each of the three t(3;5)-positive cases of AML examined. The predicted MLF1 amino acid sequence lacked homology to previously characterized proteins and did not contain known functional motifs. Normal MLF1 transcripts were expressed in a variety of tissues, most abundantly in testis, ovary, skeletal muscle, heart, kidney and colon. Anti-MLF1 antibodies detected the wild-type 31 kDa protein in K562 and HEL erythroleukemia cell lines, but not in HL-60, U937 or KG-1 myeloid leukemia lines. By contrast, t(3;5)-positive leukemia cells expressed a 54 kDa NPM-MLF1 protein, but not normal MLF1. Immunostaining experiments indicated that MLF1 is normally located in the cytoplasm, whereas NPM-MLF1 is targeted to the nucleus, with highest levels in the nucleolus. The nuclear/nucleolar localization of NPM-MLF1 mirrors that of NPM, indicating that NPM trafficking signals direct MLF1 to an inappropriate cellular compartment in myeloid leukemia cells.
在骨髓增生异常综合征和急性髓系白血病（AML）中发现的一种t(3;5)(q25.1;q34)染色体易位，导致5号染色体上的核仁磷酸蛋白（NPM）基因的一部分与3号染色体上一个新基因的序列发生重排。这些细胞表达的嵌合转录本包含5'端NPM编码序列，与新基因的编码序列框内融合，我们将这个新基因命名为骨髓增生异常/髓系白血病因子1（MLF1）。基于RNA的聚合酶链反应分析显示，在检测的三例t(3;5)阳性AML病例中，每例都存在相同的NPM-MLF1 mRNA融合。预测的MLF1氨基酸序列与先前鉴定的蛋白质缺乏同源性，也不包含已知的功能基序。正常的MLF1转录本在多种组织中表达，在睾丸、卵巢、骨骼肌、心脏、肾脏和结肠中表达最为丰富。抗MLF1抗体在K562和HEL红白血病细胞系中检测到野生型31 kDa蛋白，但在HL-60、U937或KG-1髓系白血病细胞系中未检测到。相比之下，t(3;5)阳性白血病细胞表达一种54 kDa的NPM-MLF1蛋白，而不表达正常的MLF1。免疫染色实验表明，MLF1通常位于细胞质中，而NPM-MLF1靶向细胞核，在核仁中水平最高。NPM-MLF蛋白的核/核仁定位与NPM相似，表明NPM的转运信号将MLF1导向髓系白血病细胞中不适当的细胞区室。
