Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: a Cancer and Leukemia Group B Study (8762).
Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: a Cancer and Leukemia Group B Study (8762).
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DOI：
10.1182/blood.v80.12.2983.bloodjournal80122983
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发表时间：
1992-12
期刊：
影响因子：
20.3
通讯作者：
C. Westbrook;A. Hooberman;C. Spino;R. Dodge;R. Larson;F. Davey;D. Wurster‐Hill;R. Sobol;C. Schiffer;C. Bloomfield
中科院分区：
文献类型：
--
作者：
C. Westbrook;A. Hooberman;C. Spino;R. Dodge;R. Larson;F. Davey;D. Wurster‐Hill;R. Sobol;C. Schiffer;C. Bloomfield
费城（Ph 1）染色体，或其分子对应物，BCR-ABL融合基因，是儿童急性淋巴细胞白血病（ALL）的一个罕见但重要的预后指标，但其对成人ALL的影响尚未得到很好的确定。对进入癌症和白血病组B（CALGB）进行的临床试验的患者开始了BCR-ABL融合基因的前瞻性研究。所有患者均接受了包括柔红霉素在内的强化多药化疗。在2年多的时间里，56例患者进行了研究的BCR-ABL基因的分子证据，使用Southern印迹和脉冲场凝胶杂交分析。结果进行了比较，与细胞遗传学检测的Ph 1染色体，和临床特征进行了比较，为BCR-ABL阳性和阴性组。分子方法检测BCR-ABL基因在30%的情况下，相比之下，细胞遗传学检测的Ph 1染色体只有23%。大多数病例（76%）的p190基因亚型与儿童ALL相似; BCR-ABL阳性病例的免疫表型比BCR-ABL阴性病例更为均一，主要为CALLA阳性（86%）和B细胞表面抗原阳性（82%）。BCR-ABL阳性组和阴性组的完全缓解率相似（分别为71%和77%，P = 0.72）。在BCR-ABL阳性组中有更多的早期复发，导致缓解持续时间较短，尤其是在CALLA阳性和B细胞抗原阳性人群中。这些初步数据表明，BCR-ABL基因对ALL临床结局的影响可能是维持完全缓解（CR），而不是在使用侵袭性多药化疗时实现CR。这项研究确定了BCR-ABL基因作为成人ALL的一个重要因素，并证明了其准确诊断的分子方法的实用性。
The Philadelphia (Ph1) chromosome, or its molecular counterpart, the BCR-ABL fusion gene, is a rare but important prognostic indicator in childhood acute lymphoblastic leukemia (ALL), but its impact on adult ALL has not been well ascertained. A prospective study of the BCR-ABL fusion gene was begun on patients entered on clinical trials conducted by the Cancer and Leukemia Group B (CALGB). All patients received intensive, multiagent chemotherapy that included daunorubicin. Over 2 years, 56 patients were studied for molecular evidence of a BCR-ABL gene using Southern blot and pulsed-field gel hybridization analysis. Results were compared with cytogenetic detection of a Ph1 chromosome, and clinical features were compared for the BCR-ABL-positive and -negative groups. Molecular methods detected the BCR-ABL gene in 30% of cases compared with cytogenetic detection of the Ph1 chromosome in only 23%. The majority of cases (76%) showed the p190 gene subtype similar to pediatric ALL; the BCR-ABL-positive cases displayed a more homogeneous immunophenotype than the BCR-ABL-negative cases and were predominantly CALLA positive (86%) and B-cell surface antigen positive (82%). The rate of achieving complete remission was similar in the BCR-ABL-positive and -negative groups (71% and 77%, respectively, P = .72). There were more early relapses in the BCR-ABL-positive group, resulting in a shorter remission duration that was especially marked in the CALLA-positive and B-cell antigen-positive populations. These preliminary data suggest that the impact of the BCR-ABL gene on clinical outcome in ALL may be on maintenance of complete remission (CR) rather than achievement of CR when aggressive, multiagent chemotherapy is used. This study identifies the BCR-ABL gene as an important factor in adult ALL and demonstrates the utility of molecular methods for its accurate diagnosis.