Wilms’ tumor gene 1 in hematological malignancies: friend or foe?

Wu, Jie; Yan, Hui; Xiang, Chunli

doi:10.1080/16078454.2023.2254557

Cited by 2 publications

(2 citation statements)

References 122 publications

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“…Targeted therapy for WT1 mainly involves the use of wild-type or modified major histocompatibility complex (MHC) class I restrictive WT1 peptides to produce vaccines against WT1-overexpressing tumor cells and leukemia mother cells (23). In addition, another study (24) has reported on the development of monoclonal antibodies targeting the WT1/MHC-I peptide complex expressed on the surface of leukemia mother cells. Therefore, although WT1 is well established as one of the oncogenes closely associated with tumors or leukemia, to date, few studies have reported on its important role in the targeted differentiation of leukemia.…”

Section: Discussionmentioning

confidence: 99%

“…WT1 can be used as a biomarker variously for the diagnosis of AML, monitoring of MRD, clinical management, molecular remission or recurrence detection of the disease (21,22). Furthermore, the high expression status of WT1 provides useful opportunities for the development of vaccines, targeted antibodies or chimeric antigen receptor immunotherapy (23,24). However, the exact role of WT1 in the development of leukemia remains poorly understood; moreover, the complexity associated with this function of WT1 will require a great research effort in the future (25).…”

Section: Introductionmentioning

confidence: 99%

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The up-regulation of TGF-β1 by miRNA-132-3p/WT1 is involved in inducing leukemia cells to differentiate into macrophages

Wang,

Zhang

et al. 2024

Preprint

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Although it has been shown that abnormal expression of Wilm’s tumor gene 1 (WT1) is associated with the occurrence of leukemia, the specific mechanism via which it induces leukemia cells to differentiate into macrophages remains poorly understood. Based on the prediction that the microRNA miRNA-132-3p is the miRNA that possibly lies upstream of the WT1 gene, we hypothesized that miRNA-132-3p may participate in the polarization process of macrophages through regulating expression of the WT1 gene. The focus of the present study was therefore to investigate the role of the miRNA-132-3p/WT1 signaling axis in the differentiation of THP-1 leukemia cells into macrophages induced by PMA. The results obtained indicated that, compared with the control group, the proliferation of THP-1 cells was clearly inhibited by PMA, and the cell cycle was arrested at G0/G1 phase, associated with an upregulation of CD11b and CD14 expression. Induced by PMA, the expression level of miRNA-132-3p was increased, WT1 expression was decreased, and the expression level of TGF-β1 was increased. Following transfection with miRNA-132-3p mimics, however, the expression of WT1 in the THP-1 cells was downregulated, with upregulation of the CD11b and CD14 antigens, whereas this downregulation of WT1 mediated by miRNA-132-3p mimics could be reversed by co-transfection with WT1 vector, which was accompanied by downregulation of the CD11b and CD14 antigens. The luciferase activity of the co-transfected miRNA-132-3p mimic + WT1-wild-type (WT) group was found to be statistically significantly lower compared with that of the co-transfected miRNA-132-3p mimic + WT1-mutated (MUT) group. Furthermore, chromatin immunoprecipitation experiments showed that WT1 was able to directly target the promoter of the downstream target gene TGF-β1, which led to the negative modulation of TGF-β1 expression, whereas downregulation of WT1 led to an upregulation of the expression of TGF-β1, which thereby promoted the differentiation of THP-1 cells into macrophages. Taken together, the present study has provided evidence, to the best of the authors’ knowledge for the first time, that the miRNA-132-3p/WT1/TGF-β1 axis is able to regulate the committed differentiation of leukemia cells into macrophages.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The up-regulation of TGF-β1 by miRNA-132-3p/WT1 is involved in inducing leukemia cells to differentiate into macrophages

Wang,

Zhang

et al. 2024

Preprint

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Wilms’ Tumor 1 Gene Expression as a Predictive Marker for Clinical Outcome of Acute Myeloid Leukemia in Iraqi Population: A Prospective Study

Alyaqubi,

Al-Bedariy,

Sharba

et al. 2024

Al-Rafidain J Med Sci

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Background: Wilms' tumor gene 1 (WT1), a tumor-associated antigen (TAA), is expressed in many types of cancer. Most acute leukemia patients have a quantitatively detectable and strong expression of it. Objectives: To analyze WT1 expression levels as a predictor of clinical outcomes at the time of diagnosis of de novo leukemia and to monitor tumor progression during treatment. Methods: A total of 71 patients with acute myeloid leukemia (AML) were separated into two groups: twenty-nine de novo AML patients upon presentation and 25 with AML at the time of initial induction. The second induction included 17 AML patients and ten healthy volunteers who served as controls in this study. The WT1 gene was tested using a real-time PCR with the Cyber Green assay. Results: Patients with acute myeloid leukemia had considerably greater levels of WT1 gene expression than controls (27.3 vs. 5.5). In terms of clinical outcomes, WT1 gene overexpression was substantially related to non-responsive AML patients compared to complete response at diagnosis (27.3 vs. 22.15). However, there is no substantial difference between instances following induction. Conclusions: The WT1 tumor antigen may serve as an early diagnostic for acute leukemia prognosis. Improved clinical outcomes have been linked to reduced WT1 levels. A high amount, on the other hand, was linked to a poor prognosis for people with AML, although more research is needed.

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Wilms’ tumor gene 1 in hematological malignancies: friend or foe?

Cited by 2 publications

References 122 publications

The up-regulation of TGF-β1 by miRNA-132-3p/WT1 is involved in inducing leukemia cells to differentiate into macrophages

The up-regulation of TGF-β1 by miRNA-132-3p/WT1 is involved in inducing leukemia cells to differentiate into macrophages

Wilms’ Tumor 1 Gene Expression as a Predictive Marker for Clinical Outcome of Acute Myeloid Leukemia in Iraqi Population: A Prospective Study

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