Era T, Asou N, Kunisada T, Yamasaki H, Asou H, Kamada N, Nishikawa S, Yamaguchi K, Takatsuki K
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Genes Chromosomes Cancer. 1995 May;13(1):25-33. doi: 10.1002/gcc.2870130105.
The t(8;21) is a common chromosomal abnormality, preferentially associated with acute leukemia showing features of myeloid differentiation. Recently, two genes--AML1, which has a unique runt domain, and ETO (MTG8)--have been isolated from the chromosomal breakpoint. In this study, we isolated and identified two fused transcripts from a leukemic cell line carrying t(8;21). AML1 and ETO were fused at the same position in these transcripts. One of the transcripts codes a unique domain, including two zinc finger domains and three proline- and one leucine-rich region. The other transcript codes only for one proline- and leucine-rich region but lacks zinc finger domains. We demonstrated by polymerase chain reaction (PCR) analysis that 1) these two transcripts are consistently expressed in leukemic cells with t(8;21) obtained from patients and 2) expression of AML1 was not restricted to the particular stage of hematopoietic differentiation but was present in all hematopoietic cells investigated. We also provide evidence that two wild types of ETO transcripts containing the region of the ETO gene in fused transcripts are expressed in hematopoietic cells from different lineages. The widespread expression of AML1 and ETO in hematopoietic cells suggests a fundamental role of these proteins in hematopoiesis. Furthermore, the differences in the carboxy termini of ETO may modulate the activity of fused proteins resulting from the chromosomal translocation t(8;21).
t(8;21)是一种常见的染色体异常，优先与表现出髓系分化特征的急性白血病相关。最近，从染色体断点分离出了两个基因——具有独特 runt 结构域的 AML1 和 ETO(MTG8)。在本研究中，我们从携带 t(8;21)的白血病细胞系中分离并鉴定出两种融合转录本。在这些转录本中，AML1 和 ETO 在同一位置融合。其中一种转录本编码一个独特的结构域，包括两个锌指结构域以及三个富含脯氨酸和一个富含亮氨酸的区域。另一种转录本仅编码一个富含脯氨酸和亮氨酸的区域，但缺乏锌指结构域。我们通过聚合酶链反应(PCR)分析证明：1) 这两种转录本在从患者获得的携带 t(8;21)的白血病细胞中持续表达；2) AML1 的表达并不局限于造血分化的特定阶段，而是存在于所有研究的造血细胞中。我们还提供证据表明，在融合转录本中包含 ETO 基因区域的两种野生型 ETO 转录本在来自不同谱系的造血细胞中表达。AML1 和 ETO 在造血细胞中的广泛表达表明这些蛋白质在造血过程中具有重要作用。此外，ETO 羧基末端的差异可能会调节由染色体易位 t(8;21)产生的融合蛋白的活性。
