Clonal development and karyotype evolution during leukemogenesis of BCR/ABL transgenic mice.
Clonal development and karyotype evolution during leukemogenesis of BCR/ABL transgenic mice.
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DOI：
10.1182/blood.v79.4.1029.bloodjournal7941029
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发表时间：
1992-02
期刊：
影响因子：
20.3
通讯作者：
J. Voncken;C. Morris;P. Pattengale;G. Dennert;Christie Kikly;J. Groffen;N. Heisterkamp
中科院分区：
文献类型：
--
作者：
J. Voncken;C. Morris;P. Pattengale;G. Dennert;Christie Kikly;J. Groffen;N. Heisterkamp
费城（Ph）易位负责嵌合BCR/ABL癌基因的产生。Ph染色体是慢性粒细胞白血病中最早可检测到的染色体异常，在急性淋巴细胞白血病中也有发现。转基因P190 BCR/ abl产生DNA构建体的小鼠发展为淋巴母细胞白血病/淋巴瘤，并为研究疾病的早期阶段及其进展提供了机会。在这项研究中，我们对10只19日龄BCR/ABL P190转基因小鼠的骨髓进行了核型分析，这些小鼠可再生地发生白血病/淋巴瘤。对来自17名绝症转基因创始人和后代的白血病细胞以及白血病供体骨髓移植受者的白血病细胞也进行了核型分析。在早期BCR/ABL p190产生的白血病中没有明显的染色体畸变，即使在疾病的晚期也可以发现正常的中期。在晚期白血病中发现了高频率的非整倍体，并明显倾向于小鼠染色体12、14或17的增益。这些结果表明BCR/ABL在白血病发生中的主要作用，并表明BCR/ABL基因对细胞分裂的调节具有不稳定作用。
The Philadelphia (Ph) translocation is responsible for the generation of the chimeric BCR/ABL oncogene. The Ph chromosome constitutes the earliest detectable chromosome abnormality in chronic myelogenous leukemia and is also found in acute lymphoblastic leukemia. Mice transgenic for a P190 BCR/ABL-producing DNA construct develop lymphoblastic leukemia/lymphoma and provide an opportunity to study early stages of the disease as well as progression. In this study, we have karyotyped the bone marrow of 10 19-day-old BCR/ABL P190 transgenic mice from a line that reproducibly develops leukemia/lymphoma. Leukemic cells from 17 terminally ill transgenic founders and progeny were also karyotyped as well as bone marrow transplant recipients of leukemic donor marrow. Karyotypically visible aberrations were absent from the early stages of BCR/ABL P190-generated leukemia and normal metaphases could be found even in the terminal stages of the disease. A high frequency of aneuploidy was found in advanced leukemia, with a marked preference for the gain of mouse chromosomes 12, 14, or 17. These results point to a primary role for BCR/ABL in leukemogenesis and suggest a destabilizing effect of the BCR/ABL gene on the regulation of cell division.