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[Expression of Wif-1 and β-catenin in the Wnt pathway in childhood acute lympho-blastic leukemia]
Ji-Zhao Gao1, Ji-Ou Zhao, Ying Tan
1Department of Pediatric Hematology and Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China. 843160320@qq.com.
Insights
Reduced Wnt inhibitory factor-1 (Wif-1) expression and increased β-catenin expression are linked to childhood acute lymphoblastic leukemia (ALL) pathogenesis and prognosis. These Wnt pathway alterations may drive disease development.
Area of Science:
- Oncology
- Molecular Biology
- Pediatric Hematology
Background:
- The Wnt signaling pathway plays a critical role in cellular development and is implicated in various cancers.
- Wnt inhibitory factor-1 (Wif-1) is a secreted antagonist of the Wnt pathway, while β-catenin is a key intracellular mediator.
- Dysregulation of the Wnt pathway is increasingly recognized in hematological malignancies, including acute lymphoblastic leukemia (ALL).
Purpose of the Study:
- To investigate the expression levels of Wnt inhibitory factor-1 (Wif-1) and β-catenin in pediatric patients with acute lymphoblastic leukemia (ALL).
- To explore the potential roles of Wif-1 and β-catenin in the Wnt pathway during the pathogenesis of childhood ALL.
- To correlate Wif-1 and β-catenin expression with clinical risk stratification and leukemia subtype.
Main Methods:
- Retrospective review of clinical data from 35 children with newly-diagnosed ALL and 15 controls.
- Quantitative real-time PCR (RT-PCR) to measure mRNA expression of Wif-1 and β-catenin.
- Enzyme-linked immunosorbent assay (ELISA) to determine Wif-1 protein levels.
Main Results:
- Newly diagnosed ALL patients (incipient group) exhibited significantly lower Wif-1 mRNA/protein and higher β-catenin mRNA compared to controls and remission groups.
- High-risk ALL patients showed increased β-catenin mRNA and decreased Wif-1 mRNA/protein compared to medium/low-risk patients.
- T-cell ALL cases displayed higher β-catenin mRNA and lower Wif-1 mRNA/protein than B-lineage ALL, with a negative correlation between Wif-1 and β-catenin expression.
Conclusions:
- Downregulation of Wif-1 and upregulation of β-catenin are potentially involved in the pathogenesis of childhood ALL.
- The extent of Wif-1 reduction and/or β-catenin increase may serve as indicators of prognosis in pediatric ALL.
- These findings highlight the significance of Wnt pathway modulation in childhood ALL development and progression.
Objective:
To investigate the expression and possible roles of Wnt inhibitory factor-1 (Wif-1) and β-catenin in the Wnt pathway in childhood acute lymphoblastic leukemia (ALL).
Methods:
The clinical data of 35 children who had newly-diagnosed ALL and achieved complete remission on day 33 of remission induction therapy were retrospectively reviewed. The children before treatment were considered as the incipient group, and those who achieved complete remission on day 33 were considered as the remission group. Fifteen children with non-malignant hematologic diseases were enrolled as the control group. RT-PCR was used to measure the mRNA expression of Wif-1 and β-catenin. ELISA was used to measure the protein expression of Wif-1.
Results:
Compared with the control and remission groups, the incipient group had significantly lower mRNA and protein expression of Wif-1 and significantly higher mRNA expression of β-catenin (P<0.05). In the incipient and remission groups, high-risk children showed significantly higher mRNA expression of β-catenin and significantly lower mRNA and protein expression of Wif-1 than the medium- and low-risk children (P<0.05). In the incipient and remission group, the children with T-cell acute lymphoblastic leukemia showed significantly higher mRNA expression of β-catenin and significantly lower mRNA and protein expression of Wif-1 compared with those with B-lineage acute lymphoblastic leukemia (P<0.05). In each group, there was a negative correlation between the mRNA expression of Wif-1 and β-catenin (P<0.05).
Conclusions:
Reduced expression of Wif-1 and increased expression of β-catenin may be involved in the pathogenesis of childhood ALL, and the degree of reduction in Wif-1 and/or increase in β-catenin may be related to prognosis.
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