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WT1 Expression in Circulating RNA as a Minimal Residual Disease Marker for AML Patients After Stem-Cell
Ling Zhong1, Lingling Wei, Jiao Chen
1Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, No. 1 Keyuan 4th Road, Gaopeng Avenue, Chengdu, 610041, People's Republic of China.
Background:
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).
Objective:
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.
Methods:
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.
Results:
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).
Conclusion:
Analysis of WT1 expression in CRNA in AML patients could be a simple, convenient and noninvasive method to predict latent information about relapse.
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