Morris C M, Heisterkamp N, Kennedy M A, Fitzgerald P H, Groffen J
Department of Pathology, Children's Hospital of Los Angeles, CA.
Blood. 1990 Nov 1;76(9):1812-8.
Leukemic cells from a patient with Ph-negative chronic myeloid leukemia (CML) had a normal karyotype. M-BCR was rearranged and chromosome in situ hybridization showed an ABL insertion between 5' and 3' M-BCR on an apparently normal chromosome 22. The association of 5' BCR and 3' ABL at the 5' junction of the chromosome 9 insert was typical of that found for the BCR-ABL fusion gene in other patients with the standard t(9;22) and CML. With an M-bcr-3' probe, we cloned and characterized a 3' junction fragment. Field inversion gel electrophoresis and chromosome in situ hybridization studies using a probe isolated from genomic DNA 5' of the junction showed that 3' M-BCR was joined to a region of chromosome 9q34 rich in repetitive sequences and lying some distance 3' of ABL. The chromosome 9 insert was at least 329 kilobases long and included 3' ABL and a larger portion of chromosome 9q34. Our results allowed us to exclude transposon- or retroviral-mediated insertion of ABL into chromosome 22. Instead, we favored a two-translocation model in which a second translocation reconstituted a standard t(9;22)(q34;q11) but left the chromosome 9 insert, including 3' ABL, in chromosome 22.
一名Ph阴性慢性髓性白血病（CML）患者的白血病细胞具有正常的核型。M-BCR发生重排，染色体原位杂交显示在一条明显正常的22号染色体上，ABL插入到5'和3' M-BCR之间。在9号染色体插入片段的5'连接处，5' BCR与3' ABL的关联是其他具有标准t(9;22)和CML患者中BCR-ABL融合基因的典型特征。使用M-bcr-3'探针，我们克隆并鉴定了一个3'连接片段。使用从连接点5'的基因组DNA中分离的探针进行的脉冲场凝胶电泳和染色体原位杂交研究表明，3' M-BCR与富含重复序列且位于ABL 3'端一定距离处的9号染色体q34区域相连。9号染色体插入片段至少329千碱基长，包含3' ABL和9号染色体q34的较大部分。我们的结果使我们能够排除转座子或逆转录病毒介导的ABL插入22号染色体的情况。相反，我们支持一种双易位模型，即第二次易位重新构建了标准的t(9;22)(q34;q11)，但将包含3' ABL的9号染色体插入片段留在了22号染色体中。
