Nakamura K, Miyashita T, Ozaki M, Iwaya M, Nakazawa S, Okamura J, Kamada N, Tanaka K, Kobayashi N, Mizutani S
Department of Virology, National Children's Medical Research Center, Tokyo, Japan.
Cancer. 1991 Dec 1;68(11):2426-30. doi: 10.1002/1097-0142(19911201)68:11<2426::aid-cncr2820681117>3.0.co;2-c.
Thirty-two cases of chronic myelogenous leukemia (CML) were studied to determine whether there was a correlation between the position of the chromosome breakpoint within the breakpoint cluster region (bcr) on chromosome 22 and the type of chimeric mRNA expression. One case with the chromosome breakpoint in zone 2 of the major bcr (Mbcr) and six cases with breakpoints in zone 3 expressed Mbcr exon 2-abl (b2-a) mRNA, and they were in distinguishable at the level of mRNA expression. The remaining ten cases with breakpoints in zone 3 and all ten cases with breakpoints in zone 4 expressed Mbcr exon 3-abl (b3-a) mRNA with or without b2-a mRNA. Three cases with breakpoints in zone 5 expressed b3-a mRNA, and none of these expressed Mbcr exon 4-abl(b4-a) mRNA. The cases with breakpoints in zones 4 or 5 had b3-a mRNA expression indistinguishable from those with breakpoints in zone 3. In two patients, the breakpoint in the bcr could not be determined by Southern hybridization using the 3' bcr probe or the large bcr probe. However, when analyzed for chimeric mRNA expression, both of them exhibited b3-a chimeric mRNA, suggesting the possibility that the entire Mbcr is deleted in the majority of leukemic cells in these patients. These studies indicate that Southern hybridization analysis combined with the polymerase chain reaction assay is a useful approach to understanding the pathologic role of bcr-abl gene recombination and expression in the development of CML.
对32例慢性粒细胞白血病（CML）患者进行了研究，以确定22号染色体上断裂点簇区域（bcr）内染色体断裂点的位置与嵌合mRNA表达类型之间是否存在相关性。1例主要bcr（Mbcr）2区染色体断裂点患者和6例3区断裂点患者表达Mbcr外显子2-abl（b2-a）mRNA，在mRNA表达水平上无法区分。其余10例3区断裂点患者和所有10例4区断裂点患者表达Mbcr外显子3-abl（b3-a）mRNA，有或无b2-a mRNA。3例5区断裂点患者表达b3-a mRNA，均未表达Mbcr外显子4-abl（b4-a）mRNA。4区或5区断裂点患者的b3-a mRNA表达与3区断裂点患者无法区分。在2例患者中，使用3'bcr探针或大bcr探针进行Southern杂交无法确定bcr中的断裂点。然而，在分析嵌合mRNA表达时，两者均表现出b3-a嵌合mRNA，提示这些患者大多数白血病细胞中整个Mbcr可能缺失。这些研究表明，Southern杂交分析与聚合酶链反应检测相结合是了解bcr-abl基因重组和表达在CML发生发展中病理作用的一种有用方法。
