Drabkin H A, Diaz M, Bradley C M, Le Beau M M, Rowley J D, Patterson D
Proc Natl Acad Sci U S A. 1985 Jan;82(2):464-8. doi: 10.1073/pnas.82.2.464.
Acute myelogenous leukemia (AML), subgroup M2, is associated with a nonrandom chromosomal translocation, t(8;21)(q22,q22). The oncogene c-mos also has been localized to the q22 band on chromosome 8. There is also evidence that genes on chromosome 21 may be important in the development of leukemia. To determine whether the c-mos oncogene has been translocated in AML-M2 with this translocation and to isolate DNA sequences and genes from these two chromosomes that may be important in malignancy, we constructed somatic cell hybrids between a Chinese hamster ovary cell (CHO) mutant defective in glycine metabolism and myeloblasts with an 8;21 translocation from a patient with AML. We isolated the 21q+ chromosome of this translocation in a somatic cell hybrid and showed that the c-mos oncogene had not been translocated to chromosome 21, ruling out the possibility that translocation of c-mos to chromosome 21 is necessary for development of AML-M2. In addition, there was no detectable rearrangement of the c-mos locus within a 12.4-kilobase region surrounding the gene, indicating that rearrangement of the coding region of the gene itself or alteration of proximal 5' or 3' flanking sequences is not involved. We used this hybrid to determine whether specific DNA sequences and biochemical markers from chromosomes 8 and 21 had been translocated in this case.
急性髓系白血病(AML)M2亚组与一种非随机染色体易位t(8;21)(q22,q22)相关。癌基因c-mos也定位于8号染色体的q22带。也有证据表明21号染色体上的基因在白血病发生过程中可能很重要。为了确定c-mos癌基因在伴有这种易位的AML-M2中是否发生了易位,并从这两条可能在恶性肿瘤中起重要作用的染色体上分离出DNA序列和基因,我们构建了一种体细胞杂种,该杂种由一个在甘氨酸代谢方面存在缺陷的中国仓鼠卵巢细胞(CHO)突变体和一名AML患者的具有8;21易位的成髓细胞组成。我们在一个体细胞杂种中分离出了这种易位的21q+染色体,并表明c-mos癌基因没有易位到21号染色体上,排除了c-mos易位到21号染色体是AML-M2发生所必需的可能性。此外,在该基因周围12.4千碱基区域内未检测到c-mos基因座的重排,这表明该基因编码区本身的重排或近端5'或3'侧翼序列的改变并未涉及。我们利用这种杂种来确定在这种情况下8号和21号染色体上的特定DNA序列和生化标记是否发生了易位。