Tamaki H, Ogawa H, Ohyashiki K, Ohyashiki J H, Iwama H, Inoue K, Soma T, Oka Y, Tatekawa T, Oji Y, Tsuboi A, Kim E H, Kawakami M, Fuchigami K, Tomonaga M, Toyama K, Aozasa K, Kishimoto T, Sugiyama H
Department of Pathology, Osaka University Medical School, Suita City, Japan.
Leukemia. 1999 Mar;13(3):393-9. doi: 10.1038/sj.leu.2401341.
The Wilms' tumor gene, WT1, is a tumor marker for leukemic blast cells. The WT1 expression levels were examined for 57 patients with myelodysplastic syndromes (MDS) (refractory anemia (RA), 35; RA with excess of blasts (RAEB) 14; RAEB in transformation (RAEB-t), six; and MDS with fibrosis, two) and 12 patients with acute myeloid leukemia (AML) evolved from MDS. These levels significantly increased in proportion to the disease progression of MDS from RA to overt AML via RAEB and RAEB-t in both bone marrow (BM) and peripheral blood (PB). WT1 expression levels in PB significantly correlated with the evolution of RAEB or RAEB-t to overt AML within 6 months. Therefore, WT1 expression levels in PB were superior to those in BM for early prediction of the evolution to AML by means of quantitation of the WT1 expression levels. Furthermore, WT1 expression in PB of patients with overt AML evolved from MDS was significantly decreased by effective chemotherapy or allogeneic stem cell transplantation and became undetectable in long-term survivors. These results clearly showed that WT1 expression levels are a tumor marker for preleukemic or leukemic blast cells of MDS and thus reflect the disease progression of MDS. Therefore, monitoring of WT1 expression levels has made continuous assessment of the disease progression of MDS possible, as well as the prediction of the evolution of RAEB or RAEB-t to overt AML within 6 months. The results also showed that quantitation of WT1 expression levels is useful for diagnosis of minimal residual disease of MDS with high sensitivity, thus making it possible to evaluate the efficacy of treatment for MDS.
肾母细胞瘤基因WT1是白血病原始细胞的肿瘤标志物。检测了57例骨髓增生异常综合征（MDS）患者（难治性贫血（RA）35例、伴有过多原始细胞的RA（RAEB）14例、转化中的RAEB（RAEB-t）6例、伴有纤维化的MDS 2例）以及12例由MDS演变而来的急性髓系白血病（AML）患者的WT1表达水平。在骨髓（BM）和外周血（PB）中，这些水平随着MDS从RA经RAEB和RAEB-t进展为明显的AML而显著升高。PB中的WT1表达水平与6个月内RAEB或RAEB-t演变为明显AML显著相关。因此，通过定量WT1表达水平，PB中的WT1表达水平在早期预测向AML的演变方面优于BM中的水平。此外，经有效化疗或异基因干细胞移植后，由MDS演变而来的明显AML患者PB中的WT1表达显著降低，在长期存活者中变得不可检测。这些结果清楚地表明，WT1表达水平是MDS白血病前期或白血病原始细胞的肿瘤标志物，从而反映了MDS的疾病进展。因此，监测WT1表达水平使得持续评估MDS的疾病进展以及预测6个月内RAEB或RAEB-t向明显AML的演变成为可能。结果还表明，定量WT1表达水平对高灵敏度诊断MDS微小残留病有用，从而能够评估MDS的治疗效果。
