Quantitative monitoring of BCR/ABL transcript during STI-571 therapy.
Quantitative monitoring of BCR/ABL transcript during STI-571 therapy.
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STI-571 治疗期间 BCR/ABL 转录本的定量监测。
DOI：
10.1080/1042819021000039992
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发表时间：
2002
影响因子：
2.6
通讯作者：
Ritz,Jerome
中科院分区：
文献类型：
--
作者：
Wu,CatherineJ;Neuberg,Donna;Chillemi,Antoinette;McLaughlin,Stephen;Hochberg,EphraimP;Galinsky,Ilene;DeAngelo,Daniel;Soiffer,RobertJ;Alyea,EdwinP;Capdeville,Renaud;Stone,RichardM;Ritz,Jerome
Bcr/abl融合转录本的聚合酶链式反应为检测慢性粒细胞白血病(CML)患者微小残留病提供了一种高度敏感和特异的方法。我们试图确定在接受蛋白酪氨酸激酶抑制剂STI-571治疗的情况下，外周血bcr/abl转录本的定量PCR测量是否可以用于监测临床明显疾病的CML患者的反应。对17例患者(慢性期9例，加速期或急变期8例)治疗1年后的骨髓细胞遗传学及外周血bcr/abl m RNA水平进行检测。总体而言，定量PCRbcr/abl转录水平在前3个月下降了中位数0.9log，12个月下降了1.6logs。在细胞遗传学应答者(6个CP和2个AP/BC)中，治疗3个月和12个月后，BCR/ABL拷贝数中位数分别比基线低0.9和2.1个对数。没有一例患者的bcr/abl基因扩增为阴性。在细胞遗传学无反应者中，BCR/ABL转录水平在3个月后下降了0.4logs，随后没有下降。在研究开始时，细胞遗传学应答者和无应答者的bcr/abl表达相似。治疗3个月后bcr/abl表达差异有统计学意义(p=0.02)，继续治疗6个月、9个月、12个月bcr/abl表达差异有统计学意义(p分别为0.04、0.005、0.0008)。我们的结果表明，PBMC bcr/abl mRNA水平与对STI-571的反应有很好的相关性。这种非侵入性、快速和灵敏的基于PCR的检测方法可用于监测对STI-571的反应。
PCR for the BCR / ABL fusion transcript provides a highly sensitive and specific method for detecting minimal residual disease in patients with chronic myeloid leukemia (CML). We sought to determine if quantitative PCR measurement of peripheral blood BCR / ABL transcript can be used to monitor response in CML patients with clinically evident disease while receiving the protein tyrosine kinase inhibitor STI-571. Serial bone marrow cytogenetics and peripheral blood BCR / ABL mRNA levels were measured in 17 patients [9 with chronic phase (CP) and 8 with accelerated phase or blast crisis (AP/BC)] during 1 year of treatment. Overall, quantitative PCR BCR / ABL transcript level decreased by a median of 0.9 log during the first 3 months, and by 1.6 logs by 12 months. Among cytogenetic responders (6 CP and 2 AP/BC), median BCR / ABL copy number was 0.9 and 2.1 logs lower than baseline after 3 and 12 months of treatment, respectively. No patient became PCR-negative for BCR / ABL. Among cytogenetic non-responders, BCR / ABL transcript level decreased by 0.4 logs after 3 months, with no subsequent reductions. At study entry, BCR / ABL expression in cytogenetic responders and non-responders was similar. However, BCR / ABL expression became significantly different 3 months after treatment (p =0.02), and increasingly different with continued therapy (p =0.04, 0.005, 0.0008 at 6, 9 and 12 months, respectively). Our results demonstrate that PBMC BCR / ABL mRNA levels correlate well with response to STI-571. This non-invasive, rapid and sensitive PCR-based assay can be used to monitor response to STI-571.