Shanske A L, Grunwald H, Cook P, Heisterkamp N, Groffen J
Department of Pediatrics, Center for Congenital Disorders, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY 10467, USA.
Leuk Res. 1998 Jul;22(7):645-8. doi: 10.1016/s0145-2126(98)00058-7.
Chronic myelogenous leukemia (CML) is associated with an acquired karyotypic abnormality, the Philadelphia (Ph) chromosome, in 95% of cases. The Ph chromosome is the product of a balanced translocation that results in a hybrid gene that is considered essential for the pathogenesis of this disease. We have found a complex translocation involving chromosomes 9, 12, and 15 in a 42-year-old Haitian male with the clinical findings of CML. Complex translocations have been shown to result in the masking of the Ph chromosome. We used a mixture of two BCR-specific DNA probes for Southern blot analysis in order to test this hypothesis in our patient. High-molecular weight DNA was digested with the restriction enzymes BglII, BamHI and HindIII. The BglII digestion revealed the presence of two abnormal fragments of 3.9 and 3.0 kb and the BamHI digestion an abnormal 15-kb fragment. These data suggest there is a breakpoint in region 2 of M-bcr. The identification of this breakpoint confirms our hypothesis that a rearrangement involving 22q11 has occurred in the leukemic cells of our patient. A secondary translocation involving chromosomes 12 and 15 has hidden the effects of this translocation. Combined cytogenetic and molecular analysis establishes the karyotype of our patient as 46,XY,t(9;12;15;22)(q34;q12;q21;q11).
慢性粒细胞白血病（CML）在95%的病例中与一种获得性核型异常——费城（Ph）染色体相关。Ph染色体是一种平衡易位的产物，它导致了一个融合基因的产生，该融合基因被认为是这种疾病发病机制的关键因素。我们在一名有CML临床表现的42岁海地男性患者中发现了涉及9号、12号和15号染色体的复杂易位。复杂易位已被证明会导致Ph染色体被掩盖。我们使用两种BCR特异性DNA探针的混合物进行Southern印迹分析，以便在我们的患者中验证这一假设。高分子量DNA用限制性内切酶BglII、BamHI和HindIII进行消化。BglII消化显示存在3.9 kb和3.0 kb的两个异常片段，BamHI消化显示一个15 kb的异常片段。这些数据表明在M-bcr的2区存在一个断点。这个断点的鉴定证实了我们的假设，即在我们患者的白血病细胞中发生了涉及22q11的重排。涉及12号和15号染色体的二次易位掩盖了这次易位的影响。细胞遗传学和分子分析相结合确定我们患者的核型为46,XY,t(9;12;15;22)(q34;q12;q21;q11)。
