WT1 Expression in Circulating RNA as a Minimal Residual Disease Marker for AML Patients After Stem-Cell Transplantation.

Abstract

Circulating RNA in plasma (CRNA) refers to soluble tumor-derived ribonucleic acids (RNA). The Wilms tumor 1 (WT1) gene appears to be a highly promising marker for minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients after chemotherapy or hematopoietic stem-cell transplantation (HSCT). This study aimed to compare the relative expression level of the WT1 gene in CRNA, bone marrow (BM)- and peripheral blood (PB)-RNA for the monitoring of MRD in AML patients after HSCT. One hundred and eighteen AML patients were studied with WT1 expression assessed by quantitative polymerase chain reaction in plasma, BM- and PB-RNA. Correlation analysis was used to compare gene expression differences. The expression of the WT1 gene was successfully detected in 118 cases but was absent in controls (mean relative expression of WT1/ABL 8.77, range 0.5-56.0, P < 0.001) (WT1 in BM-RNA: mean relative expression 8.66, range 0.5-56.0, P < 0.001; WT1 in PB-RNA: mean relative expression 8.55, range 0.5-54.0, P < 0.001). WT1 expression in CRNA, BM-RNA and PB-RNA showed no difference at diagnosis (CRNA vs. BM-RNA, r = 0.999; CRNA vs. PB-RNA, r = 0.988). After HSCT, 62 patients achieved remission. The expression level of WT1 in CRNA and BM-RNA in nine patients who achieved permanent remission fluctuated within the normal range (WT1/ABL < 0.02). The other 53 patients who were predicted to relapse had elevated WT1 levels in CRNA and BM-RNA. Of these 53 patients, 48 had increased expression of the WT1 gene in both CRNA and BM-RNA at a median of 1 month prior to clinical relapse. In the other five patients (5/53) diagnosed with extramedullary relapse, the level of WT1 in CRNA was elevated prior to relapse. However, in these patients WT1 expression in both BM-RNA and PB-RNA was still negative (at a median of 1 month earlier than in BM-RNA). This study indicated that CRNA was no different from BM-RNA for determination of WT1 expression in AML patients (F = 0.260, P = 0.642). Analysis of WT1 expression in CRNA in AML patients could be a simple, convenient and noninvasive method to predict latent information about relapse.