Radich J P, Kopecky K J, Boldt D H, Head D, Slovak M L, Babu R, Kirk J, Lee A, Kessler P, Appelbaum F
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Leukemia. 1994 Oct;8(10):1688-95.
The sensitivity and clinical utility of the polymerase chain reaction (PCR) assay for the detection of BCR-ABL gene rearrangement was compared to conventional cytogenetics for the Philadelphia chromosome (Ph1) in adult acute lymphoblastic leukemia (ALL) patients entered onto a single clinical trial. Ninety-three patients had evaluable PCR assays for both the p190bcr-abl and p210bcr-abl type of BCR-ABL gene rearrangements. Twenty-one of 93 patients (23%) were positive for the BCR-ABL rearrangement by the PCR assay. Fourteen of these patients had the p210brc-abl BCR-ABL rearrangement characteristically seen in CML patients, while seven had the p190bcr-abl rearrangement seen in ALL alone. Of 61 patients analyzed, both with conventional cytogenetics and PCR, eight (13%) were positive for the Ph1, while 14 (23%) were positive for the BCR-ABL rearrangement by the PCR assay. Discordance between the PCR assay and cytogenetics occurred in eight cases where the PCR assay was positive and the cytogenetics negative, and two cases where the PCR assay was negative and cytogenetics positive. PCR positivity did not correlate with treatment response, survival, or relapse-free survival, but there was a higher percentage of L2 FAB morphology in the PCR+ cases compared to the PCR-cases (67 vs. 28%, p = 0.003). In addition, the data suggested that patients with a p190bcr-abl rearrangement have a better response to induction therapy, but a worse relapse-free survival compared to patients with a p210bcr-abl breakpoint, but these differences were not statistically significant. These data suggest that PCR and conventional cytogenetics may provide complementary information, since there appear to be a subset of patients who are Ph1-negative yet BCR-ABL positive by PCR. Further studies will be required to determine the prognostic significance of the detailed information about BCR-ABL breakpoints that is available from the PCR assay.
在一项单一临床试验中，对成年急性淋巴细胞白血病（ALL）患者进行研究，比较了聚合酶链反应（PCR）检测BCR-ABL基因重排的敏感性和临床实用性与检测费城染色体（Ph1）的传统细胞遗传学方法。93例患者可进行p190bcr-abl和p210bcr-abl两种类型BCR-ABL基因重排的PCR检测。93例患者中有21例（23%）通过PCR检测BCR-ABL重排呈阳性。其中14例患者具有慢性粒细胞白血病（CML）患者典型的p210brc-abl BCR-ABL重排，而7例具有仅在ALL中出现的p190bcr-abl重排。在61例同时进行传统细胞遗传学和PCR分析的患者中，8例（13%）Ph1呈阳性，而14例（23%）通过PCR检测BCR-ABL重排呈阳性。PCR检测与细胞遗传学结果不一致的情况有8例，即PCR检测阳性而细胞遗传学检测阴性，以及2例PCR检测阴性而细胞遗传学检测阳性。PCR阳性与治疗反应、生存率或无复发生存率无关，但与PCR阴性病例相比，PCR阳性病例中L2 FAB形态的比例更高（67%对28%，p = 0.003）。此外，数据表明，与具有p210bcr-abl断点的患者相比，具有p190bcr-abl重排的患者诱导治疗反应更好，但无复发生存率更差，但这些差异无统计学意义。这些数据表明，PCR和传统细胞遗传学可能提供互补信息，因为似乎有一部分患者Ph1阴性但PCR检测BCR-ABL阳性。需要进一步研究以确定从PCR检测中获得的关于BCR-ABL断点的详细信息的预后意义。
