International Journal of Hematology and Oncology
2023, Vol 33, Num 4 Page(s): 1-7
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Aberrant Hypermethylation of APC Tumor Supressor Gene in Acute Leukemia Patients
Ozden HATIRNAZNG1, Sinem FIRTINA1, Yucel ERBILGIN1, Ugur OZBEK2, Muge SAYITOGLU1
1Istanbul University, Aziz Sancar Institution for Experimental Medical Research, Department of Genetics, , Istanbul, TURKEY
2Acıbadem University, Acıbadem Faculty of Medicine, Department of Medical Genetics, Istanbul, TURKEY
Keywords: APC, methylation, Expression, Acute leukemia, WNT signaling
Wingless Type (WNT) signaling pathway is an evolutionarily conserved pathway that is crucial for the cell fate determination, survival and expansion of lymphocyte progenitors. It has been demonstrated that deregulated WNT signaling is one of the participating mechanism underlying lymphoid leukemogenesis. Inactivating mutations and methylation in Adenomatous Polyposis Coli (APC) gene, a negative regulator of WNT pathway, can cause ligand independent WNT pathway simulation. In this study, promoter methylation and expression of the APC gene is evaluated in childhood lymphoid and myeloid acute leukemia patients (n= 118) and representative cell lines by using methylation specific PCR (MS-PCR) and real time quantitative PCR (QRT-PCR). APC gene promoter found hypermethylated in the 56% of childhood acute leukemia patients [49.2% of B-cell acute lymphoblastic leukemia (B-ALL), 62.5% of T-cell acute lymphoblastic leukemia (T-ALL) and 64.1% of Acute myeloid leukemia (AML)]. To evaluate the reflection of promoter methylation, APC mRNA levels were examined and found that all acute lymphoblastic leukemia subgroups have statistically lower APC expression levels compared to controls. Although there was no association with clinical parameters, promoter hypermethylation of APC gene seems to be a common epigenetic event in acute leukemia and leading to differential expression levels among different acute leukemia phenotypes.
Ozden HATIRNAZNG1, Sinem FIRTINA1, Yucel ERBILGIN1, Ugur OZBEK2, Muge SAYITOGLU1
1Istanbul University, Aziz Sancar Institution for Experimental Medical Research, Department of Genetics, , Istanbul, TURKEY
2Acıbadem University, Acıbadem Faculty of Medicine, Department of Medical Genetics, Istanbul, TURKEY
Keywords: APC, methylation, Expression, Acute leukemia, WNT signaling
Wingless Type (WNT) signaling pathway is an evolutionarily conserved pathway that is crucial for the cell fate determination, survival and expansion of lymphocyte progenitors. It has been demonstrated that deregulated WNT signaling is one of the participating mechanism underlying lymphoid leukemogenesis. Inactivating mutations and methylation in Adenomatous Polyposis Coli (APC) gene, a negative regulator of WNT pathway, can cause ligand independent WNT pathway simulation. In this study, promoter methylation and expression of the APC gene is evaluated in childhood lymphoid and myeloid acute leukemia patients (n= 118) and representative cell lines by using methylation specific PCR (MS-PCR) and real time quantitative PCR (QRT-PCR). APC gene promoter found hypermethylated in the 56% of childhood acute leukemia patients [49.2% of B-cell acute lymphoblastic leukemia (B-ALL), 62.5% of T-cell acute lymphoblastic leukemia (T-ALL) and 64.1% of Acute myeloid leukemia (AML)]. To evaluate the reflection of promoter methylation, APC mRNA levels were examined and found that all acute lymphoblastic leukemia subgroups have statistically lower APC expression levels compared to controls. Although there was no association with clinical parameters, promoter hypermethylation of APC gene seems to be a common epigenetic event in acute leukemia and leading to differential expression levels among different acute leukemia phenotypes.
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