ADH5/ALDH2 dehydrogenases and DNA polymerase theta protect normal and malignant hematopoietic cells from formaldehyde challenge: therapeutic implications.
Article in Leukemia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
0numbers the graph read from it
0cells of the map it votes in
6citing 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.
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.
Jessica AtkinsFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-9563-3358
Anna-Mariya KukuyanFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
Monika TomaFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0001-8414-253X
Malgorzata DrzewieckaDepartment of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Umeshkumar VekariyaFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
Adam KaramiFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
Margaret Nieborowska-SkorskaFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
Reza NejatiDepartment of Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Emir HadzijusufovicDepartment of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-7409-4204
Peter ValentDepartment of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0003-0456-5095
Tomasz StoklosaDepartment of Tumor Biology and Genetics, Medical University of Warsaw, Warsaw, Poland.ORCID 0000-0001-6918-5056
Tomasz SliwinskiDepartment of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Mariusz WasikDepartment of Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA.ORCID 0000-0002-1988-3670
Tomasz SkorskiFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA. tskorski@temple.edu.ORCID 0000-0002-3809-4538
Funding
Targeting DNA repair to eradicate TKi-refractory/resistant CML and Ph+ALLR01CA186238 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI SKORSKI, TOMASZ · 2014 to 2024
$4.5M
AML mutation-guided drugging of DNA repairR01CA237286 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI MAZIN, ALEXANDER V, SKORSKI, TOMASZ · 2020 to 2024
$2.8M
Divergent Functions of ERK Substrate Binding Domains in Pathogenesis of Myeloproliferative NeoplasmsR01CA283396 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI TOMASZ SKORSKI, DAVID L. WIEST · 2023 to 2026
$2.8M
PolQ as a novel therapeutic target in AMLR01CA244179 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI POMERANTZ, RICHARD T, SKORSKI, TOMASZ · 2020 to 2024
$2.7M
MPN-inducing mutations as biomarkers of synthetic lethalityR01CA247707 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI SKORSKI, TOMASZ · 2020 to 2024
$2.1M
Oncogenic tyrosine kinases inhibitors abrogate DNA repair and sensitive leukemias to PARP inhibitorsR01CA244044 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI SKORSKI, TOMASZ · 2020 to 2024
$1.9M
Leukemia and Lymphoma Society (Leukemia & Lymphoma Society) TRP 6628-21NCI NIH HHS R01 CA186238NCI NIH HHS R01 CA237286NCI NIH HHS R01 CA244044NCI NIH HHS R01 CA244179NCI NIH HHS R01 CA247707NCI NIH HHS R01 CA283396U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA186238U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA237286U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA244044U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA244179U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA244707
6 · The paper itself
Abstract
Normal hematopoietic stem and progenitor cells (HSPCs) are exposed to physiological levels of formaldehyde but occasionally may be challenged by high levels of formaldehyde generated by endogenous and exogenous sources. In addition, leukemia cells stressed by oncogenic mutations continuously produce excessive amounts of formaldehyde. Here, we show that DNA polymerase theta (Polθ) cooperates with alcohol dehydrogenase 5 (ADH5) and aldehyde dehydrogenase 2 (ALDH2) to protect healthy and malignant HSPCs challenged by formaldehyde. ADH5 and ALDH2 metabolize formaldehyde while Polθ-mediated DNA repair by microhomology-dependent end-joining (TMEJ) protects cells from the lethal effect of DNA double strand breaks resulting from formaldehyde-mediated DNA-protein crosslinks. Genetic or pharmacological targeting of ADH5 or ALDH2 enhanced the effect of Polθ inhibitors in leukemic cells. Thus, ADH5/ALDH2 cooperate with Polθ to protect normal HSPCs sporadically challenged by high levels of formaldehyde, and inhibition of Polθ and ADH5 or ALDH2 may exert an anti-leukemic effect.
Indexed as
Alcohol DehydrogenaseAldehyde Dehydrogenase, MitochondrialDNA-Directed DNA PolymeraseFormaldehydeHematopoietic Stem CellsAnimalsDNA Polymerase thetaHumansMiceAlcohol DehydrogenaseAldehyde Dehydrogenase, MitochondrialALDH2 protein, humanDNA-Directed DNA PolymeraseDNA Polymerase thetaFormaldehyde
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 Socratic graph.
ADH5/ALDH2 dehydrogenases and DNA polymerase theta protect normal and malignant hematopoietic cells from formaldehyde challenge: therapeutic implications. · full record | Socratic