The usefulness of monitoring WT1 gene transcripts for the prediction and management of relapse following allogeneic stem cell transplantation in acute type leukemia
The usefulness of monitoring WT1 gene transcripts for the prediction and management of relapse following allogeneic stem cell transplantation in acute type leukemia
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DOI：
10.1182/blood-2002-06-1831
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发表时间：
2003-03-01
期刊：
影响因子：
20.3
通讯作者：
Sugiyama, H
中科院分区：
文献类型：
--
作者：
Ogawa, H;Tamaki, H;Sugiyama, H
在急性白血病中，还没有建立基于微小残留病（MRD）水平的异基因干细胞移植后复发的预测方法。在本研究中，MRD在72例异基因移植的急性髓性白血病，急性淋巴细胞白血病，慢性髓性白血病（加速期或急变期）监测频繁的WT 1基因的转录，“泛白血病MRD标记”，使用逆转录酶-聚合酶链反应。基于嵌合基因表达的阴性，异基因移植后骨髓中WT 1转录本的背景水平与健康志愿者的水平相比显著降低。随着WT 1表达水平的增加，40天内复发的概率逐步增加（1.0 x 10（-2）-5.0 x 10（-2）为1100%，4.0 x 10（-3）-1.0 x 10（-2）为44.4%，4.0 x 10（-4）-4.0 x 10（-3）为10.2%，当K562中的WT 1水平定义为1.0时，< 4.0 x 10（-4）为0.8%）。复发患者的WT 1水平以恒定的倍增时间呈指数增加。在停用免疫抑制剂或输注供体白细胞有效的患者中，WT 1水平的倍增时间显著长于停用免疫抑制剂或输注供体白细胞无效的患者（P < .05）。WT 1转录物倍增时间短（< 13天）的患者对这些免疫调节治疗无反应。这些研究结果强烈表明，WT 1检测是非常有用的预测和管理复发后异基因干细胞移植，无论嵌合基因标志物的存在。
In acute-type leukemia, no method for the prediction of relapse following allogeneic stem cell transplantation based on minimal residual disease (MRD) levels is established yet. In the present study, MRD in 72 cases of allogeneic transplantation for acute myeloid leukemia, acute lymphoid leukemia, and chronic myeloid leukemia (accelerated phase or blast crisis) was monitored frequently by quantitating the transcript of WT1 gene, a "panleukemic MRD marker," using reverse transcriptase-polymerase chain reaction. Based on the negativity of expression of chimeric genes, the background level of WT1 transcripts in bone marrow following allogeneic transplantation was significantly decreased compared with the level in healthy volunteers. The probability of relapse occurring within 40 days significantly increased step-by-step according to the increase in WT1 expression level (1100% for 1.0 x 10(-2)-5.0 x 10(-2), 44.4% for 4.0 x 10(-3)-1.0 x 10(-2), 10.2% for 4.0 x 10(-4)-4.0 x 10(-3), and 0.8% for < 4.0 x 10(-4)) when WT1 level in K562 was defined as 1.0). WT1 levels in patients having relapse increased exponentially with a constant doubling time. The doubling time of the WT1 level in patients for whom the discontinuation of immunosuppressive agents or donor leukocyte infusion was effective was significantly longer than that for patients in whom it was not (P < .05). No patients with a short doubling time of WT1 transcripts (< 13 days) responded to these immunomodulation therapies. These findings strongly suggest that the WT1 assay is very useful for the prediction and management of relapse following allogeneic stem cell transplantation regardless of the presence of chimeric gene markers.