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. 2022 Dec 1;23(12):4299-4305.
doi: 10.31557/APJCP.2022.23.12.4299.

Clinical Implication of DNMT3A and TET2 Genes Mutations in Cytogenetically Normal Acute Myeloid Leukemia

Salah Aref  1 , Nahed Sallam  1 , Sherin Abd Elaziz  1 , Osama Salama  1 , Shaimaa Al Ashwah  2 , Mohamed Ayed  1
Affiliations

Clinical Implication of DNMT3A and TET2 Genes Mutations in Cytogenetically Normal Acute Myeloid Leukemia

Salah Aref et al. Asian Pac J Cancer Prev. .

Abstract

Background: Refining risk stratification of cytogenetically normal AML (CN-AML) cases is important for decision making and tailoring of therapy. In this context genetic and epigenetic mutations was considered. Among these epigenetic regulators are DNMT3A & TET2 genes. Therefore, the aim of this study was to determine the prevalence of DNMT3A and TET2 genes mutations and their impact on the outcome of adult AML patients.

Subjects and methods: The present study is cross sectional study which was conducted on 39 adult CN-AML patients at diagnosis. For all included patients sanger sequencing was done for DNMT3A exon 23 and TET2 exon 3 genes.

Results: DNMT3A mutations were detected in 8 of 39 patients (20.5%), and in 5 of 39 patients(12.8%) in TET gene. Two CN-AML patients had combined mutations in both genes. All of the mutations detected were missense and only one was frame shift. Mutated TET2 or DNMT3A genes were significantly associated with failure of complete remission (CR) (p <0.001), higher mortality rate, shorter OS (mean=16 versus 22.7 months) and shorter DFS (mean= 9.5 versus 21.4 months) when compared to non-mutated ones.

Conclusion: Mutated TET2 and DNMT3A detection define a subgroup of CN-AML patients with poor outcome.

Keywords: AML; pigenetic mutations; poor outcome.

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Conflict of interest statement

The authors declare that there is no conflict of interest to declare

Figures

Figure 1
Figure 1
A, Missense Mutation C.2645G>C in exon 23 DNMT3A with Substitution of Guanine (G) with Cytosine (C). B, Non mutated DNMT3A sequence
Figure 2
Figure 2
A, Missense Mutation C.2645G>C in exon 23 DNMT3A with Substitution of guanine (G) with cytosine (C). B, Non mutated DNMT3A sequence
Figure 3
Figure 3
OS of CN-AML Cases with TET2 or DNMT3A Mutations Versus those with no Mutations. CN-AML patients with TET2 or DNMT3A mutations had a significantly shorter OS when compared to non-mutated (P=0.046)
Figure 4
Figure 4
DFS of CN-AML Cases with TET2 or DNMT3A Mutations Versus those with no Mutations. CN-AML patients with TET2 or DNMT3A mutations had a significantly shorter DFS when compared to non-mutated ones (P=0.006)
Figure 5
Figure 5
OS of AML Cases with TET2 and DNMT3A Mutations. Single mutation, TET2 or DNMT3A mutation; double mutations; TET2 and DNMT3A mutations. No significant differences were found between AML patients had single and those had double mutations with mortality rate and OS among studied AML cases (p=0.142).
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