Hypomethylating agents increase L1 retroelement expression without inducing novel insertions in myeloid malignancies.

ABSTRACT: Retroelements in the human genome are silenced via multiple mechanisms, including DNA methylation, to prevent their potential mutagenic effect. Retroelement activity, demonstrated by their expression and somatic retrotransposition events, was shown to be deregulated in multiple tumors but not yet in leukemia. We hypothesized that treatment with hypomethylating agents, commonly used in myelodysplastic syndromes and acute myeloid leukemia, could lead to increased retroelement activity and somatic retrotranspositions, thus contributing to disease progression. To address this hypothesis, we induced the expression of ORF1p protein with hypomethylating agents in DAMI and HL-60 myeloid cell lines. To study whether long-term hypomethylating agent therapy induces somatic retrotranspositions, we ana

SUBMITTER: Pavlova S 

PROVIDER: S-EPMC12515712 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature