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Article

Polθ activity modulates sensitivity to standard therapies in DNMT3A-deficient leukemia.

Cell reports. Medicine - 17 Mar 2026

Le Bac Viet, Vekariya Umeshkumar, Toma Monika M, Nieborowska-Skorska Margaret, Caron Marie-Christine, Gozdecka Malgorzata, Haydar Zayd, Walsh Martin, Ghosh Jayashri, Vaughan-Williams Elaine, Podszywalow-Bartnicka Paulina, Kukuyan Anna-Mariya, Ziolkowska Sylwia, Atkins Jessica, Hadzijusufovic Emir, Chandramouly Gurushankar, Nejati Reza, Piwocka Katarzyna, Pomerantz Richard, Vassiliou George S, Huntly Brian J P, Valent Peter, Wasik Mariusz, Bellacosa Alfonso, Masson Jean-Yves, Gupta Gaorav P, Challen Grant A, Skorski Tomasz

Abstract excerpt

Myeloid malignancies carrying somatic DNMT3A mutations (DNMT3Amut) are refractory to standard therapy. DNMT3Amut leukemia cells accumulate toxic DNA double-strand breaks (DSBs) and stalled replication forks, rendering them dependent on DNA damage response (DDR). We report here that DNA polymerase theta (Polθ), a key element in DSB repair by end-joining (Polθ-mediated end-joining [TMEJ]) and in fork restarting,...

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Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Share to DNA Breaks, Double-Stranded

Share to DNA (Cytosine-5-)-Methyltransferases

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Source

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Identifiers

PMID: 41850232
DOI: 10.1016/j.xcrm.2026.102687
PMCID: PMC13006424

Genes

DNMT3A
PARP1
FLT3
MSH2
MSH3
SMARCAD1
UBE2O

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 8 Sept 2026.

Related research

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Research trail→

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Polθ activity modulates sensitivity to standard therapies in DNMT3A-deficient leukemia.PMID 41850232Read ↗

DNA polymerase theta-mediated DNA repair is a functional dependency and therapeutic vulnerability in DNMT3A deficient leukemia cellsSemantic proximity Read ↗

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Excess Polθ functions in response to replicative stress in homologous recombination-proficient cancer cellsSemantic proximity Read ↗

Mutations in the DNMT3A DNA methyltransferase in acute myeloid leukemia patients cause both loss and gain of function and differential regulation by protein partnersSemantic proximity Read ↗

DNMT3A Harboring Leukemia-Associated Mutations Directs Sensitivity to DNA Damage at Replication Forks.Semantic proximity Read ↗

Beyond PARP—POLθ as an anticancer targetSemantic proximity Read ↗

Targeting the DNA Repair Enzyme Polymerase θ in Cancer TherapySemantic proximity Read ↗

Polymerase theta is a synthetic lethal target for killing Epstein-Barr virus lymphomasSemantic proximity Read ↗

POLθ prevents MRE11-NBS1-CtIP-dependent fork breakage in the absence of BRCA2/RAD51 by filling lagging-strand gapsSemantic proximity Read ↗

APOBEC3A-Induced DNA Damage Drives Polymerase θ Dependency and Synthetic Lethality in CancerSemantic proximity Read ↗

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