Quantitative assessment of WT1 gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemia
Quantitative assessment of WT1 gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemia
复制标题
DOI：
10.1111/j.1600-0609.2008.01158.x
复制
发表时间：
2009-01-01
影响因子：
3.1
通讯作者：
Fanin, Renato
中科院分区：
文献类型：
--
作者：
Candoni, Anna;Tiribelli, Mario;Fanin, Renato
WT1过表达在包括急性髓性白血病（AML）在内的几种肿瘤疾病中都有报道。骨髓样本中WT1的定量可能有助于作为微小残留病（MRD）的标志物，并可能预测同种异体造血干细胞移植（HSCT）后AML的复发。在38例AML患者（男性16例，女性22例）诊断时、移植时和同种异体造血干细胞移植后（精确时间点）测量WT1的定量表达。所有病例在诊断时均显示高WT1表达水平，平均为4189 (SD 3325)，中位数为3495（范围454-13923）个WT1/10(4)Abl拷贝。移植时，25名患者（66%）完全细胞学缓解（CcR）， 13名患者（34%）患有难治性或复发性AML。与复发或难治性AML患者的骨髓样本相比，CcR移植患者的骨髓样本在HSCT期间的WT1表达水平显著降低（P = 0.004）。在所有达到或维持CcR的患者中，HSCT后WT1表达水平迅速下降。38例患者中有6例（13%）在HSCT后复发，所有患者在复发时或复发前WT1表达均升高。这6例患者中有5例死于白血病，1例通过供体淋巴细胞输注(DLI) + WT1水平迅速降低的化疗成功地重新诱导。此外，我们发现WT1表达水平与其他疾病标志物（如有）完全一致。根据我们的经验，在同种异体造血干细胞移植前后，WT1表达水平（通过定量RT-PCR在精确时间点测量）与AML状态之间存在完全的一致性。WT1可作为监测MRD的非特异性白血病标志物和AML临床复发的预测因子。基于这些结果，HSCT后WT1水平升高且无移植物抗宿主病的病例可能是停止免疫抑制和/或DLI治疗的候选人。
WT1 overexpression is described in several oncological diseases including acute myeloid leukemia (AML). Quantification of WT1 in bone marrow samples may be useful as a marker of minimal residual disease (MRD) and may predict the relapse of AML after allogeneic hematopoietic stem cell transplant (HSCT).The quantitative expression of WT1 was measured in 38 AML patients (16 males and 22 females) at diagnosis, at the time of transplant and after the allogeneic HSCT (at precise time points). All cases showed high WT1 expression levels at diagnosis with a mean of 4189 (SD 3325) and a median of 3495 (range 454-13923) copies WT1/10(4)Abl. At transplant, 25 patients (66%) were in complete cytologic remission (CcR) and 13 (34%) had refractory or relapsed AML. Bone marrow samples from patients transplanted in CcR showed significantly lower WT1 expression levels during HSCT compared with the samples from patients with a relapsed or refractory AML (P = 0.004). After HSCT, a rapid decline in WT1 expression levels was observed in all patients who attained or maintained a condition of CcR. Six of 38 patients (13%) relapsed after HSCT and all of them had an increase in WT1 expression at/or before relapse. Five of these six patients died of leukemia and one was successfully reinduced with donor lymphocyte infusion (DLI) + chemotherapy with a rapid reduction of WT1 levels. Besides, we found a complete concordance between WT1 expression levels and other disease markers (when available).In our experience, there was a complete concordance between WT1 expression levels (measured by quantitative RT-PCR at precise time points) and status of AML before and after allogeneic HSCT. WT1 may be useful as a non-specific leukemia marker for monitoring MRD and as a predictor of AML clinical relapse. Based on these results, cases with increase of WT1 levels after HSCT and without graft vs. host disease may be candidate to discontinuation of immunosuppression and/or DLI therapy.