ArticleJournal of translational medicine2020
WT1 facilitates the self-renewal of leukemia-initiating cells through the upregulation of BCL2L2: WT1-BCL2L2 axis as a new acute myeloid leukemia therapy target.
Article in Journal of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Isolation and Characterization of 5-(1-Hydroxyethyl)-Dihydro-2-Furanone fromInternational journal of molecular sciences · 2026Article
- WT1 as a Biomarker in Myelodysplastic Neoplasms: Clinical Correlations and Preliminary Data from an Iranian Cohort.International journal of hematology-oncology and stem cell research · 2026Article
- Sophoraflavanone G from Phit-Sanat (Sophora Exigua Craib) inhibits WT1 protein expression and induces cell cycle arrest and apoptosis in acute myeloid leukemia.BMC complementary medicine and therapies · 2025Article
- ST2/IL-33 axis blockade inhibits regulatory T cell cytotoxicity towards CD8 T cells in the leukemic niche.Nature communications · 2025Article
- Dual targeting of tumoral cells and immune microenvironment by blocking the IL-33/IL1RL1 pathway.Nature communications · 2025Article
- Anticancer and cancer preventive activities of shogaol and curcumin from Zingiberaceae family plants in KG-1a leukemic stem cells.BMC complementary medicine and therapies · 2025Article
- Wilms' tumor 1 (WT1) antigen is overexpressed in Kaposi Sarcoma and is regulated by KSHV vFLIP.PLoS pathogens · 2024Article
- Prognostic value of the WT-1 gene combined with recurrent cytogenetic genes in acute myeloid leukemia.Immunogenetics · 2023Article
- Article
- High prevalence of Wilms tumor 1 expression in multiple myeloma and plasmacytoma: A cohort of 142 Asian patients' samples.Pathology oncology research : POR · 2023Article
- WT1 β'ing catenin into shape: a new interaction driving epigenetic plasticity in acute myeloid leukemia?Haematologica · 2023Article
- Crosstalk between β-catenin and WT1 signaling activity in acute myeloid leukemia.Haematologica · 2023Article
- Targeting β-catenin in acute myeloid leukaemia: past, present, and future perspectives.Bioscience reports · 2022Review
- Deubiquitinases in hematological malignancies.Biomarker research · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundOverexpression of Wilms' tumor-1 (WT1) transcription factor facilitates proliferation in acute myeloid leukemia (AML). However, whether WT1 is enriched in the leukemia-initiating cells (LICs) and leukemia stem cells (LSCs) and facilitates the self-renewal of LSCs remains poorly understood.
methodsMLL-AF9-induced murine leukemia model was used to evaluate the effect of knockdown of wt1 on the self-renewal ability of LSC. RNA sequencing was performed on WT1-overexpressing cells to select WT1 targets. Apoptosis and colony formation assays were used to assess the anti-leukemic potential of a deubiquitinase inhibitor WP1130. Furthermore, NOD/SCID-IL2Rγ (NSG) AML xenotransplantation and MLL-AF9-induced murine leukemia models were used to evaluate the anti-leukemogenic potential of WP1130 in vivo.
resultsWe found that wt1 is highly expressed in LICs and LSCs and facilitates the maintenance of leukemia in a murine MLL-AF9-induced model of AML. WT1 enhanced the self-renewal of LSC by increasing the expression of BCL2L2, a member of B cell lymphoma 2 (BCL2) family, by direct binding to its promoter region. Loss of WT1 impaired self-renewal ability in LSC and delayed the progression of leukemia. WP1130 was found to modify the WT1-BCL2L2 axis, and WP1130-induced anti-leukemic activity was mediated by ubiquitin proteasome-mediated destruction of WT1 protein. WP1130 induced apoptosis and decreased colony formation abilities of leukemia cells and prolonged the overall survival in the THP1-based xenograft NSG mouse model. WP1130 also decreased the frequency of LSC and prolonged the overall survival in MLL-AF9-induced murine leukemia model. Mechanistically, WP1130 induced the degradation of WT1 by positively affecting the ubiquitination of WT1 protein.
conclusionsOur results indicate that WT1 is required for the development of AML. WP1130 exhibits anti-leukemic activity by inhibiting the WT1-BCL2L2 axis, which may represent a new acute myeloid leukemia therapy target.
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