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[Expression of Ikaros and FUT4 in Children's Acute Lymphoblastic Leukemia and Their Relationship]
Li-Jun Yi1, Hong Li2, Zhi-Bing Guo2
1Medical School of Nanchang University,Nanchang 330006,Jiangxi Province,China.Jiangxi Provincial Children's Hospital,Nanchang 330006,Jiangxi Province,China.
Objective:
To explore the possible molecular mechanism of Ikaros regulation on FUT4 expression by analyzing the correlation of the functional state of Ikaros with level of FUT4 expression, so as to provide the theoretical basis for personalized treatment in children with ALL.
Methods:
The subtypes of Ikaros were identified by nested PCR and sequencing. The expression level of FUT4 was detected by quantitative PCR and analyzed by ΔΔCt method in the early stage of treatment, remission and relapse of ALL.
Results:
Ik1 and Ik2 were the main functional subtypes, and the dominant negative Ikaros was Ik6; the Ik6 was detected in 23 patients with ALL. It was found that 2.73% patients expressing Ik6 alone and 18.18% patients with heterozygous expression were detected. The expression of FUT4 in the newly diagnosed ALL was higher than that in the control group, and the functional Ikaros negatively correlated with the FUT4 expression(r=-0.6329).
Conclusion:
Dominant negative Ikaros closely correlated with the relapse of acute lymphoblastic leukemia in children. The functional Ikaros negatively correlated with FUT4 expression. Ikaros inhibit the transcriptional activity of FUT4, that may be the molecular mechanism of Ikaros regulating the expression of FUT4.
Insights
Dominant negative Ikaros (Ik6) is linked to relapse in childhood acute lymphoblastic leukemia (ALL). Functional Ikaros inhibits FUT4 expression, suggesting a molecular mechanism for Ikaros regulation in ALL.
Area of Science:
- Molecular biology
- Oncology
- Pediatric hematology
Background:
- Acute lymphoblastic leukemia (ALL) is a common childhood cancer.
- Ikaros is a transcription factor involved in hematopoiesis and leukemia development.
- FUT4 is a gene implicated in cancer progression.
Purpose of the Study:
- To investigate the molecular mechanism of Ikaros regulation on FUT4 expression in childhood ALL.
- To analyze the correlation between Ikaros functional states and FUT4 expression levels.
- To provide a theoretical basis for personalized ALL treatment.
Main Methods:
- Identification of Ikaros subtypes using nested PCR and sequencing.
- Quantification of FUT4 expression via quantitative PCR and the ΔΔCt method.
- Analysis of Ikaros-FUT4 correlation in ALL patients at different treatment stages.
Main Results:
- Ik1 and Ik2 were identified as main functional Ikaros subtypes, with Ik6 as the dominant negative form.
- Dominant negative Ikaros (Ik6) was detected in 23 ALL patients.
- FUT4 expression was elevated in newly diagnosed ALL compared to controls, and functional Ikaros negatively correlated with FUT4 expression (r=-0.6329).
Conclusions:
- Dominant negative Ikaros (Ik6) is closely associated with relapse in pediatric ALL.
- Functional Ikaros negatively correlates with FUT4 expression.
- Ikaros likely inhibits FUT4 transcriptional activity, elucidating a key regulatory mechanism in ALL.