Hayakawa A, Matsuda Y, Daibata M, Nakamura H, Sano K
Department of Pediatrics, Kobe University School of Medicine, Kobe, Japan.
Genes Chromosomes Cancer. 2001 Apr;30(4):364-74. doi: 10.1002/gcc.1102.
We previously identified the AF3p21 gene, a novel fusion partner of the MLL gene, in a patient who had developed therapy-related leukemia with t(3;11)(p21;q23). The AF3p21 gene encodes a protein consisting of 722 amino acids, which has an SH3 (Src homology 3) domain, a proline-rich domain, and a bipartite nuclear localization signal. The protein's SH3 domain has high homology with that of FYN. Analysis of the DNA from the patient's leukemic cells revealed that intron 6 of the MLL gene was fused at a point upstream of exon 1 in the AF3p21 gene, and that the der(11) chromosome formed an MLL-AF3p21 fusion transcript in leukemic cells, whereas the der(3) chromosome did not form any fusion transcript. The AF3p21 gene on chromosome band 3p21 is 19 kb long and consists of 13 exons. The size of the mRNA of the AF3p21 gene is approximately 3.5 kb. The AF3p21 gene is widely expressed in normal human tissues including the bone marrow, brain, liver, thymus, lung, and skeletal muscle. Western blot and immunocytochemical analyses showed that AF3p21 protein has an apparent molecular weight of 80 kDa and is localized exclusively in the cell nucleus. These results suggest the possibility that AF3p21 protein plays a role in signal transduction in the nucleus.
我们之前在一名患有 t(3;11)(p21;q23) 治疗相关白血病的患者中鉴定出 AF3p21 基因，它是 MLL 基因的一个新的融合伴侣。AF3p21 基因编码一种由 722 个氨基酸组成的蛋白质，该蛋白质具有一个 SH3（Src 同源 3）结构域、一个富含脯氨酸的结构域和一个双分型核定位信号。该蛋白质的 SH3 结构域与 FYN 的 SH3 结构域具有高度同源性。对患者白血病细胞的 DNA 分析显示，MLL 基因的内含子 6 在 AF3p21 基因外显子 1 上游的一个位点处融合，并且 der(11) 染色体在白血病细胞中形成了 MLL-AF3p21 融合转录本，而 der(3) 染色体未形成任何融合转录本。染色体带 3p21 上的 AF3p21 基因长 19 kb，由 13 个外显子组成。AF3p21 基因的 mRNA 大小约为 3.5 kb。AF3p21 基因在包括骨髓、脑、肝、胸腺、肺和骨骼肌在内的正常人体组织中广泛表达。蛋白质免疫印迹和免疫细胞化学分析表明，AF3p21 蛋白的表观分子量为 80 kDa，并且仅定位于细胞核。这些结果提示 AF3p21 蛋白可能在细胞核信号转导中发挥作用。
