Uzunel M, Ringdén O
Department of Clinical Immunology, Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.
Bone Marrow Transplant. 2004 Jan;33(1):47-52. doi: 10.1038/sj.bmt.1704296.
After allogeneic stem cell transplantation (SCT), we evaluated the use of the Wilms' tumor gene (WT1) as a minimal residual disease (MRD) marker in 32 patients (28 chronic myeloid leukemia, three acute lymphoblastic leukemia and one acute myeloid leukemia). All patients expressed BCR-ABL and the kinetics of WT1 were compared with those of BCR-ABL using real-time quantitative PCR. WT1 expression was seen in the peripheral blood (PB) of healthy controls with a median expression level of 7 x 10(-5) (WT1/ABL ratio). The corresponding values for BCR-ABL-negative and BCR-ABL-positive patient samples were 1 x 10(-4) and 1.6 x 10(-4), respectively. Kinetic studies in individual patients showed that WT1 and BCR-ABL levels usually did not copy each other. In four out of six patients who relapsed, an increase in WT1 from the background level (10(-4)) was observed only at the time of or after relapse, and in two patients increasing WT1 levels were observed before the relapse. In addition, the WT1 values found at the time of relapse were only two logs higher than the background level, indicating a sensitivity of 10(-2). In conclusion, there is a constitutive low expression of WT1 in normal hematopoietic cells. The sensitivity and ability of WT1 to predict a relapse were poor in this study.
在异基因干细胞移植（SCT）后，我们评估了32例患者（28例慢性髓性白血病、3例急性淋巴细胞白血病和1例急性髓性白血病）中Wilms瘤基因（WT1）作为微小残留病（MRD）标志物的应用情况。所有患者均表达BCR-ABL，并使用实时定量PCR将WT1的动力学与BCR-ABL的动力学进行比较。在健康对照者的外周血（PB）中可检测到WT1表达，中位表达水平为7×10⁻⁵（WT1/ABL比值）。BCR-ABL阴性和阳性患者样本的相应值分别为1×10⁻⁴和1.6×10⁻⁴。对个体患者的动力学研究表明，WT1和BCR-ABL水平通常并不相互匹配。在6例复发患者中的4例中，仅在复发时或复发后观察到WT1从背景水平（10⁻⁴）升高，而在2例患者中，在复发前观察到WT1水平升高。此外，复发时测得的WT1值仅比背景水平高两个对数，表明灵敏度为10⁻²。总之，正常造血细胞中存在WT1的组成性低表达。在本研究中，WT1预测复发的灵敏度和能力较差。
