EXPRESSION OF A DISTINCTIVE BCR-ABL ONCOGENE IN PH1-POSITIVE ACUTE LYMPHOCYTIC-LEUKEMIA (ALL)
EXPRESSION OF A DISTINCTIVE BCR-ABL ONCOGENE IN PH1-POSITIVE ACUTE LYMPHOCYTIC-LEUKEMIA (ALL)
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DOI：
10.1126/science.3422516
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发表时间：
1988-02-12
期刊：
影响因子：
56.9
通讯作者：
WITTE, ON
中科院分区：
文献类型：
--
作者：
CLARK, SS;MCLAUGHLIN, J;WITTE, ON
费城染色体 (Ph1) 是 9 号和 22 号染色体之间的易位，常见于慢性粒细胞白血病 (CML) 和部分急性淋巴细胞白血病 (ALL) 患者。在 CML 中，这会导致编码 P210BCR-ABL 酪氨酸激酶的嵌合 8.5 KB BCR-ABL 转录物的表达。 ALL 中的 Ph1 染色体表达一种独特的 ABL 衍生的 7 KB 信使 RNA，编码 P185ALL-ABL 蛋白。由于不同癌基因产物的表达可能在 Ph1 阳性 ALL 与 CML 的独特表现中发挥作用，因此有必要了解 P185ALL-ABL 表达的分子基础。 P210BCR-ABL 和 P185ALL-ABL 均可被针对两种蛋白质氨基末端区域中的 BCR 决定簇的抗血清识别。 CML 中靠近 BCR-ABL 连接处的 BCR 决定簇的抗血清免疫沉淀 P210BCR-ABL，但不沉淀 P185ALL-ABL。对由 Ph1 阳性 ALL SUP-B15 细胞系的 RNA 制成的互补 DNA 克隆进行核苷酸序列分析，以及 S1 核酸酶保护分析证实 Ph1 阳性 ALL 细胞中存在 BCR-ABL 嵌合转录物。在 Ph1 阳性 ALL 中，ABL 序列与 BCR 序列在 CML 连接处 5'' 处约 1.5 kb 处连接。 P185ALL-ABL 代表 Ph1 阳性 ALL 中 BCR-ABL 融合基因的产物，与 CML 中的 BCR-ABL 融合基因不同。
The Philadelphia chromosome (Ph1) is a translocation between chromosomes 9 and 22 that is found in chronic myelogenous leukemia (CML) and a subset of acute lymphocytic leukemia patients (ALL). In CML, this results in the expression of a chimeric 8.5-kilobase BCR-ABL transcript that encodes the P210BCR-ABL tyrosine kinase. The Ph1 chromosome in ALL expresses a distinct ABL-derived 7-kilobase messenger RNA that encodes the P185ALL-ABL protein. Since the expression of different oncogene products may play a role in the distinctive presentation of Ph1-positive ALL versus CML, it is necessary to understand the molecular basis for the expression of P185ALL-ABL. Both P210BCR-ABL and P185ALL-ABL are recognized by an antiserum directed to BCR determinants in the amino-terminal region of both proteins. Antisera to BCR determinants proximal to the BCR-ABL junction in CML immunoprecipitated P210BCR-ABL but not P185ALL-ABL. Nucleotide sequence analysis of complementary DNA clones made from RNA from the Ph1-positive ALL SUP-B15 cell line, and S1 nuclease protection analysis confirmed the presence of BCR-ABL chimeric transcripts in Ph1-positive ALL cells. In Ph1-positive ALL, ABL sequences were joined to BCR sequences approximately 1.5 kilobases 5'' of the CML junction. P185ALL-ABL represents the product of a BCR-ABL fusion gene in Ph1-positive ALL that is distinct from the BCR-ABL fusion gene of CML.