Eisenberg A, Silver R, Soper L, Arlin Z, Coleman M, Bernhardt B, Benn P
Lifecodes Corporation, Valhalla, NY 10595.
Leukemia. 1988 Oct;2(10):642-7.
Rearrangement of the breakpoint cluster region (bcr) was demonstrated by Southern blot analysis in the DNA in each of 68 patients with Ph chromosome-positive CML and in 3 of 7 patients with apparent Ph chromosome-negative CML. In contrast, no bcr rearrangement could be found in DNA from 17 normal individuals and 28 patients with various hematologic disorders other than CML or ALL. An analysis of the location of the breakpoints within the bcr indicated that 3' breakpoints were significantly more common in patients in blast crisis or accelerated phase disease compared to those with chronic phase disease. Patients with chronic phase disease and 3' breakpoints had shorter average disease duration than that for chronic phase patients with 5' breakpoints, although the difference between these two groups of patients was not statistically significant. For patients who had progressed to accelerated disease or blast crisis, a statistically significant difference in chronic phase disease duration could be demonstrated between 11 patients with 3' breakpoints (average chronic phase 30.2 months) and 15 patients with 5' breakpoints (average chronic phase 50.6 months). For 8 patients studied in both chronic phase and accelerated or blast crisis, the location of the breakpoint did not change. We suggest that the bcr-abl fusion protein associated with a 3' breakpoint could result in more rapid progression to acute disease, and this may account for differences in the relative frequency of 3' and 5' breakpoints at different disease stages. Although more studies are required, identifying CML patients with a higher propensity for early blast transformation may eventually prove to be of some clinical value.
通过Southern印迹分析，在68例Ph染色体阳性慢性粒细胞白血病（CML）患者的每例DNA中以及7例看似Ph染色体阴性CML患者的3例DNA中均证实了断裂点簇集区（bcr）的重排。相比之下，在17名正常个体以及28例患有除CML或急性淋巴细胞白血病（ALL）以外的各种血液系统疾病的患者的DNA中未发现bcr重排。对bcr内断裂点位置的分析表明，与慢性期疾病患者相比，处于急变期或加速期疾病的患者中3'端断裂点明显更为常见。尽管两组慢性期患者之间的差异无统计学意义，但具有3'端断裂点的慢性期疾病患者的平均病程短于具有5'端断裂点的慢性期患者。对于已进展为加速期疾病或急变期的患者，在11例具有3'端断裂点的患者（平均慢性期30.2个月）和15例具有5'端断裂点的患者（平均慢性期50.6个月）之间，慢性期疾病持续时间存在统计学上的显著差异。对于在慢性期以及加速期或急变期均进行研究的8例患者，断裂点的位置没有改变。我们认为，与3'端断裂点相关的bcr-abl融合蛋白可能导致更快地进展为急性疾病，这可能解释了不同疾病阶段3'端和5'端断裂点相对频率的差异。尽管需要更多的研究，但识别具有早期急变倾向较高的CML患者最终可能证明具有一定的临床价值。
