TRANSLOCATION OF C-ABL ONCOGENE CORRELATES WITH THE PRESENCE OF A PHILADELPHIA-CHROMOSOME IN CHRONIC MYELOCYTIC-LEUKEMIA
TRANSLOCATION OF C-ABL ONCOGENE CORRELATES WITH THE PRESENCE OF A PHILADELPHIA-CHROMOSOME IN CHRONIC MYELOCYTIC-LEUKEMIA
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DOI：
10.1038/306277a0
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发表时间：
1983-01-01
期刊：
影响因子：
64.8
通讯作者：
GROFFEN, J
中科院分区：
文献类型：
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作者：
BARTRAM, CR;DEKLEIN, A;GROFFEN, J
肿瘤特异性染色体畸变断裂点附近的细胞癌基因的定位表明这些基因参与肿瘤的产生1，2。最近，我们证实了慢性粒细胞白血病（CML）中Abelson鼠白血病病毒（A-MuLV）转化序列的人类细胞同源物（c-abl）从9号染色体易位到费城染色体（Ph 1）。为了探讨这种易位在CML发病机制中的意义，我们现在研究了两名CML患者的复杂翻译，t（9; 11; 22）和t（1; 9; 22），和两名CML Ph 1阴性患者明显正常的核型。除了用人c-ab探针和啮齿类动物与CML细胞杂交的DNA进行印迹杂交外，我们还用这些探针直接与CML患者的中期染色体进行原位杂交。这些研究表明，c-ab基因易位在Ph 1阳性，但不是在Ph 1阴性的CML患者。没有Ph 1染色体的CML似乎是一个不同起源的独特实体，这一观点得到了临床观察的支持，包括揭示更差的预后的相关性4，5。
The localization of cellular oncogenes near the break points of tumour-specific chromosomal aberrations suggests an involvement of these genes in the generation of neoplasms1,2. Recently, we demonstrated3the translocation of the human cellular homologue (c-abl) of the transforming sequence of Abelson murine leukaemia virus (A-MuLV) from chromosome 9 to the Philadelphia chromosome (Ph1) in chronic myelocytic leukaemia (CML). In an attempt to investigate the significance of this translocation in the pathogenesis of CML, we have now studied two CML patients with complex translations, t(9; 11; 22) and t(1; 9; 22), and two CML Ph1-negative patients with apparently normal karyotypes. In addition to using blot hybridization with human c-ablprobes and DNA from Rodent: CML cell hybrids as before, we have usedin situhybridization of these probes directly to metaphase chromosomes of CML patients. These studies show that the c-ablgene is translocated in Ph1-positive but not in Ph1-negative CML patients. CML without the Ph1chromosome seems to be a distince entity with a different origin, and this view is supported by clinical observations including correlations which reveal a poorer prognosis4,5.