Evidence map›Paper›PMID 42273916›Full record

ArticleNucleic acids research2026

Sustained PRC1.1 activity preserves gene repression independently of PRC2.2 and restrains leukemic cell differentiation.

Fatemeh Mojallali, Alessandra De Meis, Sinne G Alkema, Tjerk Jan Atsma, Shanna M Hogeling, Rianne Kloosterman, Eve Ioannou, Albertus T J Wierenga, Gerwin Huls, Joost H A Martens and 2 more

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

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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

12 authors.

Fatemeh MojallaliDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.ORCID 0000-0003-0742-4335
Alessandra De MeisDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.ORCID 0009-0005-5899-9528
Sinne G AlkemaDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.ORCID 0000-0002-2463-5196
Tjerk Jan AtsmaDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.
Shanna M HogelingDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.
Rianne KloostermanDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.
Eve IoannouDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.
Albertus T J WierengaDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.
Gerwin HulsDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.
Joost H A MartensDepartment of Molecular Biology, Faculty of Science and Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands.
Jan Jacob SchuringaDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.
Vincent van den BoomDepartment of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZGroningen, The Netherlands.ORCID 0000-0002-1992-9608

Funding

Dutch Cancer Foundation KWF 11013Dutch Cancer Foundation KWF 12725Dutch Cancer Foundation KWF 15286Dutch Cancer Society
6 · The paper itself

Abstract

Loss-of-function mutations in BCOR, a subunit of the non-canonical Polycomb Repressive Complex 1.1 (PRC1.1), are frequently observed in acute myeloid leukemia (AML) and associate with adverse risk. Paradoxically, leukemic stem cell viability in BCOR wild-type AMLs strongly depends on PRC1.1 activity. Here, we use BCOR and KDM2B degron models to study PRC1.1 dependency in leukemic cells and find that BCOR is a bridging factor tethering the catalytic and chromatin-binding moieties of the PRC1.1 complex. BCOR degradation induces a quick localized loss of H2AK119ub at PRC1.1 target genes, whereas PRC2-induced H3K27me3 remains unaffected. Degron-mediated depletion of BCOR or KDM2B induces a rapid but time-dependent transcriptional induction, whereby late-upregulated genes are more heavily decorated with H3K27me3 compared to early-upregulated genes. Combined PRC1.1 inactivation and PRC2 inhibition further amplifies gene induction, suggesting collaborative yet distinct control over target genes. Strikingly, both JARID2/AEBP2 and SUZ12 knockout cells, devoid of PRC2.2 or PRC2.1/PRC2.2 respectively, retain PRC1.1 loss-induced transcriptional activation, underscoring that PRC1.1 can repress target genes independently of a downstream PRC2.2-canonical PRC1 repressive axis. Finally, combined targeting of PRC1.1 and PRC2 induces differentiation of leukemic cells, emphasizing that co-targeting PRC1.1 and PRC2 represents a promising strategy to improve treatment of AML patients.

Indexed as

Cell DifferentiationGene Expression Regulation, LeukemicLeukemia, Myeloid, AcutePolycomb Repressive Complex 1Polycomb Repressive Complex 2Proto-Oncogene ProteinsRepressor ProteinsCell Line, TumorDegronsHistonesHumansJumonji Domain-Containing Histone DemethylasesBCOR protein, humanHistonesJARID2 protein, humanJumonji Domain-Containing Histone DemethylasesPolycomb Repressive Complex 1Polycomb Repressive Complex 2Proto-Oncogene ProteinsRepressor Proteins

Identifiers

PMID42273916
PMCPMC13259592

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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.