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Updated: Jun 4, 2026
Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
[Minimal residual disease with wt1 gene expression blocked by wt1 antisense oligonucleotides in vitro]
Lu Yang1, Yue-An Cao, Chao-Sheng Peng
1Department of Special Necd, Navy General Hospital, Beijing 100037, China.
Abstract:
The aim of this study was to investigate the expression of wt1 gene and the changes of gene expression in minimal residual disease (MRD) models (K562, HL-60 cell lines) and acute leukemia (AL) patients through inhibiting the expression of wt1 gene by antisense oligonucleotides (ASO). The bone marrow (BM) of 56 AL patients with complete remission (CR) was collected, then the BM samples with positive expression of wt1 gene were screened by RT-PCR. The cells of MRD model and screened wt1 gene positive samples were cultured and treated by ASO, then the changes of wt1 gene expression were detected. The results indicated that the sensitivity of wt1 gene was 10(-3)-10(-4), and the positive rate of BM wt1 gene expression in 56 AL patients with CR was 16%. After BM of 9 AL CR patients with MRD and MRD model (K562, HL-60 cells) expressing wt1 gene were treated by ASO, it was found that the wt1 expression in ASO group was blocked, while wt1 gene could be still detected in both sense oligonucleotides (SO) and control groups. It is concluded that ASO can obstruct the expression of wt1 gene on the residual leukemia cells in vitro.
Insights
Antisense oligonucleotides (ASO) effectively block wt1 gene expression in minimal residual disease models and acute leukemia patients. This targeted inhibition shows promise for controlling residual leukemia cells in vitro.
Area of Science:
- Molecular Biology
- Oncology
Context:
- Minimal residual disease (MRD) in acute leukemia (AL) poses a challenge for achieving long-term remission.
- The WT1 gene is implicated in leukemogenesis and is a potential marker for MRD.
Purpose:
- To investigate the efficacy of antisense oligonucleotides (ASO) in inhibiting WT1 gene expression in MRD models and AL patient samples.
- To evaluate the impact of WT1 gene inhibition on residual leukemia cells.
Summary:
- WT1 gene expression was analyzed in bone marrow samples from 56 AL patients in complete remission (CR) and in K562/HL-60 cell lines.
- ASO treatment successfully blocked WT1 gene expression in vitro in MRD models and in 9 AL CR patients with detectable WT1 expression, while control groups showed persistent WT1 detection.
- The sensitivity of WT1 gene detection was 10(-3)-10(-4), with a 16% positive rate in AL CR patients.
Impact:
- ASO demonstrates potential as a therapeutic strategy to target and eliminate residual leukemia cells by inhibiting WT1 gene expression.
- This study provides in vitro evidence for the feasibility of using ASO for MRD management in acute leukemia.
