WT1 Expression in Circulating RNA as a Minimal Residual Disease Marker for AML Patients After Stem-Cell Transplantation
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ORIGINAL RESEARCH ARTICLE
WT1 Expression in Circulating RNA as a Minimal Residual Disease Marker for AML Patients After Stem-Cell Transplantation Ling Zhong1,2 • Lingling Wei3 • Jiao Chen4 • Xiaobing Huang4 • Yuping Gong5 Yanrong Lu1
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Ó Springer International Publishing Switzerland 2015
Abstract 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
Electronic supplementary material The online version of this article (doi:10.1007/s40291-015-0147-2) contains supplementary material, which is available to authorized users. & Yanrong Lu [email protected] 1
Key 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
2
Department of Clinical and Experimental Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu 610072, People’s Republic of China
3
Center for Cell Transplantation, Institute of Organ Transplantation, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu 610072, People’s Republic of China
4
Department of Hematology, Sichuan Academy of Medical Science and Sichuan Provincial Peoples’ Hospital, Chengdu 610072, People’s Republic of China
5
Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China
(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
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