Evidence map›Paper›PMID 42919848›Full record

ArticleCommunications biology2026

Targeting Artemis sensitizes acute lymphoblastic leukemia cells to topoisomerase 2 poisons by disrupting DNA-PKcs-dependent repair.

Melissa L Folkerts, Cameron Hom, Angie T M Nguyen, Kaiyuan V Shen, Alyssa M Monterroso, Ellianna M Damozonio, Alejandra Aguilar-Quintero, Valeria Rangel, Pedro Ortega, Selma Masri and 4 more

Abstract read
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In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Melissa L FolkertsDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0009-0009-9657-6146
Cameron HomDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.
Angie T M NguyenDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-9200-3510
Kaiyuan V ShenDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0009-0007-1224-8811
Alyssa M MonterrosoDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.
Ellianna M DamozonioDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0009-0002-0138-1303
Alejandra Aguilar-QuinteroDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.
Valeria RangelDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA.
Pedro OrtegaDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0003-4216-3695
Selma MasriDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-8619-8331
Noritaka AdachiGraduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.ORCID http://orcid.org/0000-0002-1895-0747
Rémi BuissonDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-7196-8209
Katheryn MeekDepartment of Microbiology, Genetics, and Immunology, Michigan State University, East Lansing, MI, USA.ORCID http://orcid.org/0000-0002-0454-4414
Nicholas R PannunzioDivision of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA. nrpann@hs.uci.edu.ORCID http://orcid.org/0000-0002-8290-8236

Funding

Rapid detection of CRLF2 rearrangements in Hispanic Ph-like ALL patients to access diagnosis and relapseR37CA266042 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Nicholas Pannunzio · 2022 to 2026
$2.5M
Aberrant V(D)J recombination in B cells initiates lymphoid malignancyR01CA276470 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Nicholas Pannunzio · 2024 to 2026
$1.0M
U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01 CA276470U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R37 CA266042
6 · The paper itself

Abstract

Topoisomerase 2 (Top2) poisons are widely used in cancer therapy but are associated with toxicity and secondary malignancies. Top2 adduct removal requires endonuclease activity prior to repair of the resulting DNA double-strand break (DSB). We show that the non-homologous end joining (NHEJ) enzyme Artemis is a key player in the process and a major target for treatment of human B-cell acute lymphoblastic leukemia (ALL). An Artemis knockout is sensitive to etoposide treatment at nanomolar levels and has significantly more unrepaired DNA DSBs. Inhibition of the Artemis activator, DNA-dependent Protein Kinase Catalytic Subunit (DNA-PKcs), acts synergistically with Top2 poisons to further sensitize ALL cells. Genetic loss of Artemis ablates this synergy underscoring its critical role in this drug interaction. Furthermore, Artemis loss results in a significant accumulation of covalent Top2A DNA adducts following etoposide treatment and a significant increase in unrepaired DNA DSBs. As clinical data demonstrate that high Artemis expression correlates with poor survival in several cancers, our work may unlock new avenues for the treatment of aggressive cancers.

Indexed as

DNA-Activated Protein KinaseDNA-Binding ProteinsDNA RepairDNA Topoisomerases, Type IIEndonucleasesNuclear ProteinsPrecursor Cell Lymphoblastic Leukemia-LymphomaTopoisomerase II InhibitorsCell Line, TumorDNA Breaks, Double-StrandedDNA End-Joining RepairEtoposideHumansPoly-ADP-Ribose Binding ProteinsDCLRE1C protein, humanDNA-Activated Protein KinaseDNA-Binding ProteinsDNA Topoisomerases, Type IIEndonucleasesEtoposideNuclear ProteinsPoly-ADP-Ribose Binding ProteinsPRKDC protein, humanTOP2A protein, humanTopoisomerase II Inhibitors

Identifiers

PMID42919848

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.