Azanucleoside treatment leads to B-cell precursor acute lymphoblastic leukemia.

ABSTRACT: 5-Aza-4'-thio-2'-deoxycytidine (ATC) is an azanucleoside cytidine analog under investigation in preclinical studies for solid tumors as a promising DNA methyltransferase 1 (DNMT1) inhibitor. Repeated treatment with ATC has previously been shown to induce acute lymphoblastic leukemia (ALL) of both B-cell and T-cell origin in mice. Herein, RAG-1 deficient or "knockout" (KO) mice (B6.129S7-RAG-1tm1Mom/J) were treated with ATC to determine if ATC could be oncogenic in nonlymphoid cells. However, ATC treatment targeted early B progenitors and invariably led to B-lineage ALL, with a gene expression signature similar to human B-cell precursor (BCP)-ALL. Whole-exome sequencing revealed numerous single base substitutions of cytosine, primarily C>G transversions at CpG dinucleotides, within genes im

SUBMITTER: Negi V 

PROVIDER: S-EPMC12555782 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature