Competitive polymerase chain reaction to estimate the number of BCR-ABL transcripts in chronic myeloid leukemia patients after bone marrow transplantation.
Competitive polymerase chain reaction to estimate the number of BCR-ABL transcripts in chronic myeloid leukemia patients after bone marrow transplantation.
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DOI：
10.1182/blood.v82.6.1929.bloodjournal8261929
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发表时间：
1993-09
期刊：
影响因子：
20.3
通讯作者：
Nicholas C. P. Cross;Lin Feng;A. Chase;J. Bungey;T. Hughes;J. Goldman
中科院分区：
文献类型：
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作者：
Nicholas C. P. Cross;Lin Feng;A. Chase;J. Bungey;T. Hughes;J. Goldman
我们开发了一种竞争性聚合酶链反应（PCR）滴定法，用于估计慢性髓性白血病患者骨髓移植（BMT）后BCR-ABL转录本的数量，以监测骨髓移植（BMT）后的微小残留疾病。该分析给出了可重复的结果，并允许区分BCR-ABL信息水平的半个数量级的差异。在91例非定量PCR研究的患者中，28例移植后至少一次PCR结果阳性的患者采用竞争性PCR分析。17例患者在观察期间骨髓无细胞遗传学复发迹象；在这些病例中，BCR-ABL转录本数约为10至800/微克RNA。11例复发患者中的10例在首次在骨髓中检测到philadelphia阳性中期时进行了细胞遗传学研究；转录数范围从1,600到7 × 10(5)/微克RNA。血液学复发的患者有9 × 10(4)到10(6)个BCR-ABL转录物/微克RNA。从细胞遗传学缓解到细胞遗传学复发再到血液学复发的患者，其血液中BCR-ABL转录物的数量增加。3例患者在常规检测细胞遗传学复发前，BCR-ABL转录物数量明显上升。相反，没有细胞遗传学复发的患者通常转录本数量低或下降。我们的结论是，通过估计BCR-ABL转录本的数量，对bmt后残留疾病的连续监测比传统的细胞遗传学或非定量PCR提供了更多的信息，并可能在明显复发之前确定需要治疗干预的患者。
We have developed a competitive polymerase chain reaction (PCR) titration assay that estimates the number of BCR-ABL transcripts in chronic myeloid leukemia patients to monitor minimal residual disease after bone marrow transplantation (BMT). The assay gave reproducible results and allowed differences in BCR-ABL message levels of half an order of magnitude to be distinguished. Of 91 patients studied by nonquantitative PCR, 28 who had a positive PCR result on at least one occasion posttransplant were analyzed by competitive PCR. Seventeen patients had no evidence in their marrow of cytogenetic relapse during the period of observation; BCR-ABL transcript numbers in these cases ranged from approximately 10 to 800/micrograms RNA. Ten of the 11 patients who relapsed cytogenetically were studied when Philadelphia-positive metaphases were first detected in their marrow; transcript numbers ranged from 1,600 to 7 x 10(5)/micrograms RNA. Patients in hematologic relapse had between 9 x 10(4) and 10(6) BCR-ABL transcripts/micrograms RNA. Patients who progressed from cytogenetic remission to cytogenetic relapse and then to hematologic relapse had increasing numbers of BCR-ABL transcripts in their blood. Three patients had clear evidence of rising numbers of BCR-ABL transcripts before routine detection of cytogenetic relapse. Conversely patients without cytogenetic relapse generally had low or falling numbers of transcripts. We conclude that serial monitoring of residual disease post-BMT by estimating the number of BCR-ABL transcripts provides more information than conventional cytogenetics or nonquantitative PCR and may identify patients in need of therapeutic intervention before the onset of overt relapse.