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

Mol Diagn Ther. 2015 Aug;19(4):205-12. doi: 10.1007/s40291-015-0147-2.

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 (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics*
  • Bone Marrow / metabolism
  • Case-Control Studies
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute / blood*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / surgery
  • Male
  • Middle Aged
  • Neoplasm, Residual / blood
  • Neoplasm, Residual / genetics*
  • RNA, Neoplasm / blood*
  • Recurrence
  • Treatment Outcome
  • WT1 Proteins / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • RNA, Neoplasm
  • WT1 Proteins
  • WT1 protein, human