Gale R P, Canaani E
Proc Natl Acad Sci U S A. 1984 Sep;81(18):5648-52. doi: 10.1073/pnas.81.18.5648.
Chronic myelogenous leukemia (CML) is a clonal hematologic malignancy characterized by a reciprocal translocation between chromosomes 9 and 22 [t(9;22)] in greater than 90% of cases. This translocation results in a short chromosome 22, termed the Philadelphia (Ph1 or 22q-) chromosome. Recently, the cellular oncogenes abl and sis were mapped to human chromosomes 9 and 22, respectively. Moreover, abl was shown to be translocated from chromosome 9 to 22 and sis from chromosome 22 to 9 in CML patients with t(9;22). These findings raised the possibility that one or both of these oncogenes is activated and directly involved in the development of the disease. We analyzed expression of the abl and sis oncogenes in leukemic cells from CML patients with t(9;22). We found that sis is not expressed but that abl is transcribed into an 8-kilobase RNA. This abl RNA is also present in two leukemic cell lines (EM2 and K562), which were derived from CML patients and contain the t(9;22). This 8-kilobase RNA is not detected in normal cells, in other human leukemias without t(9;22), or in human cell lines that lack t(9;22). The consistent presence of this abl RNA transcript in CML with t(9;22) suggests that it is a consequence of abl translocation and that it plays a role in the development of this leukemia.
慢性粒细胞白血病(CML)是一种克隆性血液系统恶性肿瘤,超过90%的病例中存在9号和22号染色体之间的相互易位[t(9;22)]。这种易位导致形成一条短的22号染色体,即费城(Ph1或22q-)染色体。最近,细胞癌基因abl和sis分别被定位到人类9号和22号染色体上。此外,在患有t(9;22)的CML患者中,发现abl从9号染色体易位到22号染色体,而sis从22号染色体易位到9号染色体。这些发现增加了以下可能性,即这些癌基因中的一个或两个被激活并直接参与疾病的发展。我们分析了患有t(9;22)的CML患者白血病细胞中abl和sis癌基因的表达。我们发现sis不表达,但abl转录成一种8千碱基的RNA。这种abl RNA也存在于两个白血病细胞系(EM2和K562)中,这两个细胞系源自CML患者并含有t(9;22)。在正常细胞、其他没有t(9;22)的人类白血病或缺乏t(9;22)的人类细胞系中未检测到这种8千碱基的RNA。在患有t(9;22)的CML中持续存在这种abl RNA转录本表明它是abl易位的结果,并且它在这种白血病的发展中起作用。