In one paragraphArticle in Science advances, 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
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 registryThe 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 literatureWho cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
4 · The recordCorrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what moneyAuthors and funding
29 authors.
Nesteene Joy ParamCenter for OncoGenomics and Innovative Therapeutics (COGIT); Center for Therapeutics Discovery, Department of Oncological Sciences and Pharmacological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY, New York, USA.ORCID 0000-0002-4276-7563 Elisa ArceciCenter for OncoGenomics and Innovative Therapeutics (COGIT); Center for Therapeutics Discovery, Department of Oncological Sciences and Pharmacological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY, New York, USA.ORCID 0000-0001-9962-7513 Francesco FiorentinoDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy.ORCID 0000-0003-3550-1860 Luca PignataInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.ORCID 0000-0002-4903-8160 Denis TorreCenter for OncoGenomics and Innovative Therapeutics (COGIT); Center for Therapeutics Discovery, Department of Oncological Sciences and Pharmacological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY, New York, USA.ORCID 0000-0003-4615-223X Nayeli Gutiérrez-TrejoCenter for OncoGenomics and Innovative Therapeutics (COGIT); Center for Therapeutics Discovery, Department of Oncological Sciences and Pharmacological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY, New York, USA.ORCID 0000-0002-3057-8167 Jia Yi FongInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
Pierre-Alexis GoyInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.ORCID 0000-0002-0281-0889 Brenda Y HanInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.ORCID 0000-0002-3212-875X Chiara LambonaDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy.
Elisabetta Di BelloDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy.
Carola CastielloDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy.
Megan SchwarzCenter for OncoGenomics and Innovative Therapeutics (COGIT); Center for Therapeutics Discovery, Department of Oncological Sciences and Pharmacological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY, New York, USA.
Dave Keng Boon WeeInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
Steven NdoyeCenter for OncoGenomics and Innovative Therapeutics (COGIT); Center for Therapeutics Discovery, Department of Oncological Sciences and Pharmacological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY, New York, USA.ORCID 0009-0006-3539-4881 Tommaso TabaglioInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.ORCID 0000-0001-6873-3073 Anand D JeyasekharanCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.ORCID 0000-0001-9816-6137 Manikandan LakshmananInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.ORCID 0000-0001-5103-3054 Roberto CirilliCentre for the Control and Evaluation of Medicines, Chemical Medicines Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Hansjörg HabischGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.ORCID 0000-0001-5537-506X Tobias MadlGottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.ORCID 0000-0002-9725-5231 Sergio ValenteDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy.ORCID 0000-0002-2241-607X Antonello MaiDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy.ORCID 0000-0001-9176-2382 Ernesto GuccioneCenter for OncoGenomics and Innovative Therapeutics (COGIT); Center for Therapeutics Discovery, Department of Oncological Sciences and Pharmacological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY, New York, USA.ORCID 0000-0001-7764-5307 Funding
No grant is acknowledged in the PubMed record.
6 · The paper itselfAbstract
Acute myeloid leukemia (AML) is a hematopoietic malignancy caused by abnormal proliferation and differentiation of blasts. PRMT5, a methyltransferase that catalyzes symmetric dimethylation of arginine (SDMA) residues, has been implicated in cancer stem cell homeostasis and shown to be a potential therapeutic target in AML. However, given the toxicity of complete PRMT5 inhibition, there is a need to identify effective synergistic therapies. Through a targeted screen of compounds that inhibit key nodes of PRMT5-regulated pathways, we identified a synthetic lethality between inhibition of PRMT5 and LSD1, a lysine demethylase known to affect AML blast differentiation. The two inhibitors broadly reshape the transcriptome of targeted cells and synergize to promote AML differentiation and eventually growth inhibition and apoptosis, in a p53-dependent manner. To leverage this synthetic lethal interaction, we generated new dual compounds to inhibit both enzymes and recapitulated the effects of the drug combination. Our results uncover an unexpected convergence of PRMT5- and LSD1-regulated targets, paving the way for new therapeutic opportunities.
Indexed as
Enzyme InhibitorsHistone DemethylasesLeukemia, Myeloid, AcuteProtein-Arginine N-MethyltransferasesApoptosisCell DifferentiationCell Line, TumorCell ProliferationDrug SynergismHumansTumor Suppressor Protein p53Enzyme InhibitorsHistone DemethylasesKDM1A protein, humanPRMT5 protein, humanProtein-Arginine N-MethyltransferasesTumor Suppressor Protein p53
Identifiers
PMID41894488
PMCPMC13025030
What OpenQuestion holds
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