Daley G Q, Van Etten R A, Baltimore D
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
Science. 1990 Feb 16;247(4944):824-30. doi: 10.1126/science.2406902.
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.
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）指导合成P210bcr/abl蛋白。P210bcr/abl的蛋白酪氨酸激酶活性和杂交结构与艾贝尔森鼠白血病病毒的癌基因产物P160gag/v-abl相似，后者可诱发急性淋巴瘤。为了确定P210bcr/abl是否能诱发慢性粒细胞白血病，将编码P210bcr/abl的逆转录病毒感染小鼠骨髓，并移植到经辐照的同基因受体中。移植受体发生了几种血液系统恶性肿瘤；其中最突出的是一种骨髓增殖综合征，与人类慢性粒细胞白血病的慢性期极为相似。患病小鼠的肿瘤组织含有编码P210bcr/abl的前病毒。这些结果表明，P210bcr/abl的表达可诱发慢性粒细胞白血病。该蛋白的逆转录病毒介导表达为进一步分析该疾病提供了一个小鼠模型系统。
