慢性髓系白血病患者移植造血干细胞后bcr/abl融合基因变化的实时定量RT-PCR监测及其意义

Detection of bcr/abl Fusion Gene Changes in Patients with Chronic Myeloid Leukemia after allo-HSCT by Real-time Quantitative Reverse Transcription Polymerase Chain Reaction and Its Significance

为了探讨Ph阳性慢性髓系白血病(CML)患者异基因造血干细胞移植后不同时期bcr/abl融合基因水平变化的实时定量PCR监测及其意义,对21例CML患者骨髓移植后不同时期bcr/abl融合基因水平用实时定量PCR技术进行了连续监测。结果表明:21例bcr/abl融合基因阳性CML患者移植后7例未检测出融合基因,14例移植后1-6月仍可检出不同水平bcr/abl融合基因。动态观察发现,9例bcr/abl融合基因处于较低水平,相对数在0.0074%-0.088%,于移植后第3-7月转为阴性。5例符合分子生物学复发标准,融合基因相对数在0.077%-75%。其中1例在骨髓移植后1、2、3个月融合基因相对数分别为0.95%、1.5%、0.16%,于移植后4个月自行转阴性;2例接受同一供者单个核细胞输注后bcr/abl转为阴性;2例发展为临床血液学复发,其中1例经化疗及同供者单个核细胞输注再次缓解,但bcr/abl阳性,另1例不治死亡。结论:对于ph阳性CML患者骨髓移植后连续定量监测bcr/abl融合基因水平可以了解疾病残留状态,预测分子学生物学复发,指导临床治疗,并评价疗效。

t This study was aimed to detect the changes of bcr/able gene level in ph ^＋ CML patients at different stages after allo-HSCT by real-time quantitative PCR and to evaluate the significance of this detection. The serial detection of bcr/abl fusion gene levels in 21 cases of CML treated with allo-HSCT was performed by RQ-PCR. The results showed that the bcr/able fusion gene could not be detected in 7 out 21 CML cases with positive fusion gene after allo-HSCT, while the bcr/abl fusion gene of different levels could be detected in 14 cases within 1 - 6 months. Dynamic detection indicated that the bcr/abl fusion gene levels in 9 cases were lower with relative value 0.0074% -0.088% and then could not be detected within 3 - 7 months after alIo-HSCT. The bcr/abl fusion gene levels in 5 cases diagnosed as molecular relapse were between 0.077% - 75%. The bcr/abl fusion gene levels in 1 out of 5 cases were 0.95%, 1.5%, and 0. 16% in month 1,2 and 3, respectively, and turned to negative in the month 4 without any treatment after allo-HSCT. 2 cases received the donor peripheral blood stem cell infusion, and then their bcr/abl mRNA levels could not be detected in bone marrow. Another 2 cases developed to the hematologic relapse, 1 out of 2 cases reached CR again after infusion of donor peripheral blood stem cells and chemotherapy, the other one died. It is concluded that serial quantifications of bcr/abl mRNA levels by RQ-PCR are reliable and can be used to detect the MRD, to monitor the outcome and to predict the relapse.