INDUCTION OF CHRONIC MYELOGENOUS LEUKEMIA IN MICE BY THE P210BCR/ABL GENE OF THE PHILADELPHIA-CHROMOSOME
INDUCTION OF CHRONIC MYELOGENOUS LEUKEMIA IN MICE BY THE P210BCR/ABL GENE OF THE PHILADELPHIA-CHROMOSOME
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DOI：
10.1126/science.2406902
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发表时间：
1990-02-16
期刊：
影响因子：
56.9
通讯作者：
BALTIMORE, D
中科院分区：
文献类型：
--
作者：
DALEY, GQ;VANETTEN, RA;BALTIMORE, D
在几乎所有慢性粒细胞白血病患者的肿瘤细胞中，费城染色体（9号和22号染色体的融合体）指导P210 bcr/abl蛋白的合成。P210 bcr/abl的蛋白酪氨酸激酶活性和杂合结构类似于Abelson鼠白血病病毒的癌基因产物P160 gag/v-abl，其诱导急性淋巴瘤。为了确定P210 bcr/abl是否可以诱导慢性粒细胞白血病，用编码P210 bcr/abl的逆转录病毒感染小鼠骨髓，并移植到辐射的同基因受体中。移植受者发生了几种恶性血液病，其中最突出的是骨髓增生综合征，与人类慢性粒细胞白血病的慢性期非常相似。结果表明，P210 bcr/abl基因的表达可诱导慢性粒细胞白血病的发生。逆转录病毒介导的蛋白质表达为进一步分析该疾病提供了鼠模型系统。
In tumor cells from virtually all patients with chronic myelogenous leukemia, the Philadelphia chromosome, a fusion of chromosomes 9 and 22, directs the synthesis of the P210bcr/abl protein. The protein-tyrosine kinase activity and hybrid structure of P210bcr/abl are similar to the oncogene product of the Abelson murine leukemia virus, P160gag/v-abl, which induces acute lymphomas. To determine whether P210bcr/abl can induce chronic myelogenous leukemia, murine bone marrow was infected with a retrovirus encoding P210bcr/abl and transplanted into irradiated syngeneic recipients. Transplant recipients developed several hematologic malignancies; prominent among them was a myeloproliferative syndrome closely resembling the chronic phase of human chronic myelogenous leukemia. Tumor tissue from diseased mice harbored the provirus encoding P210bcr/abl. These results demonstrate that P210bcr/abl expression can induce chronic myelogenous leukemia. Retrovirus-mediated expression of the protein provides a murine model system for further analysis of the disease.