Evaluation of Wilms’ Tumor (WT1) Gene Methylation in Acute Lymphocytic Leukemia Patients
AbstractBackground: Leukemia is the most common type of childhood cancer, with acute lymphoblastic leukemia being the most common subtype among children. Epigenetic factors, such as DNA methylation, are found to be important in leukemia. According to the National Cancer Institute, Wilms’ tumor (WT1) is among the most important tumor antigens. This study examines WT1 gene methylation as a diagnostic or therapeutic method in patients afflicted by ALL. Methods: 37 ALL patients were enrolled in this study before initiation of treatment. Twelve healthy subjects were used as the control group. After DNA extraction and conversion with bisulfite, WT1 gene methylation in samples was analyzed via the MSP technique. Results: The WT1 gene promoter was not methylated in patients or the control group. Conclusion: Due to the absence of WT1 gene promoter methylation in patients, as well as the healthy group, it is likely that methylation of the promoter of this gene is of no consequence in leukemia development, and subsequently cannot aid in its diagnosis.
2. McNeer JL, Bleyer A. Acute lymphoblastic leukemia and lymphoblastic lymphoma in adolescents and young adults. Pediatr Blood Cancer. 2018;65:e26989.
3. Burke MJ, Bhatla T. Epigenetic modifications in pediatric acute lymphoblastic leukemia. Front Pediatr. 2014;2:42.
4. Florean C, Schnekenburger M, Grandjenette C, Dicato M, Diederich M. Epigenomics of leukemia: from mechanisms to therapeutic applications. Epigenomics. 2011;3:581-609.
5. Ramos KN, Ramos IN, Zeng Y, Ramos KS. Genetics and epigenetics of pediatric leukemia in the era of precision medicine. F1000Res. 2018;7.
6. Toska E, Roberts SG. Mechanisms of transcriptional regulation by WT1 (Wilms’ tumour 1). Biochem J. 2014;461:15-32.
7. Li X, Li Y, Yuan T, et al. Exogenous expression of WT1 gene influences U937 cell biological behaviors and activates MAPK and JAK-STAT signaling pathways. Leuk res. 2014;38:931-9.
8. Van Driessche A, Berneman ZN, Van Tendeloo VF. Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials. oncologist. 2012;17: 250–259.
9. Figueroa ME, Chen SC, Andersson AK, et al. Integrated genetic and epigenetic analysis of childhood acute lymphoblastic leukemia. J Clin Invest 2013;123:3099-111.
10. Busse A, Gökbuget N, Siehl JM, et al. Wilms’ tumor gene 1 (WT1) expression in subtypes of acute lymphoblastic leukemia (ALL) of adults and impact on clinical outcome. Ann Hematol. 2009;88:1199.
11. Loeb DM, Evron E, Patel CB, et al. Wilms’ tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation. Cancer research. 2001;61:921-5.