Evidence map›Paper›PMID 34497325›Full record

ArticleLeukemia2022

Insufficiency of non-canonical PRC1 synergizes with JAK2V617F in the development of myelofibrosis.

Daisuke Shinoda, Yaeko Nakajima-Takagi, Motohiko Oshima, Shuhei Koide, Kazumasa Aoyama, Atsunori Saraya, Hironori Harada, Bahityar Rahmutulla, Atsushi Kaneda, Kiyoshi Yamaguchi and 6 more

Abstract read
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In one paragraph

Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 33% of its field
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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
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

16 authors at 6 institutions in 1 country.

Daisuke ShinodaDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yaeko Nakajima-TakagiDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Motohiko OshimaDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Shuhei KoideDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Kazumasa AoyamaDepartment of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Atsunori SarayaDepartment of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hironori HaradaLaboratory of Oncology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Bahityar RahmutullaDepartment of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Atsushi KanedaDepartment of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.ORCID http://orcid.org/0000-0002-6980-5515
Kiyoshi YamaguchiDivision of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yoichi FurukawaDivision of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Haruhiko KosekiLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Kazuya ShimodaDivision of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.ORCID http://orcid.org/0000-0002-2555-8188
Tomoaki TanakaDepartment of Molecular Diagnosis, Chiba University Graduate School of Medicine, Chiba, Japan.
Goro SashidaLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.ORCID http://orcid.org/0000-0003-2318-5987
Atsushi IwamaDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. 03aiwama@ims.u-tokyo.ac.jp.ORCID http://orcid.org/0000-0001-9410-8992
Chiba University · JPThe University of Tokyo · JPKumamoto University · JPRIKEN Center for Integrative Medical Sciences · JPTokyo University of Pharmacy and Life Sciences · JPUniversity of Miyazaki · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Insufficiency of polycomb repressive complex 2 (PRC2), which trimethylates histone H3 at lysine 27, is frequently found in primary myelofibrosis and promotes the development of JAK2V617F-induced myelofibrosis in mice by enhancing the production of dysplastic megakaryocytes. Polycomb group ring finger protein 1 (Pcgf1) is a component of PRC1.1, a non-canonical PRC1 that monoubiquitylates H2A at lysine 119 (H2AK119ub1). We herein investigated the impact of PRC1.1 insufficiency on myelofibrosis. The deletion of Pcgf1 in JAK2V617F mice strongly promoted the development of lethal myelofibrosis accompanied by a block in erythroid differentiation. Transcriptome and chromatin immunoprecipitation sequence analyses showed the de-repression of PRC1.1 target genes in Pcgf1-deficient JAK2V617F hematopoietic progenitors and revealed Hoxa cluster genes as direct targets. The deletion of Pcgf1 in JAK2V617F hematopoietic stem and progenitor cells (HSPCs), as well as the overexpression of Hoxa9, restored the attenuated proliferation of JAK2V617F progenitors. The overexpression of Hoxa9 also enhanced JAK2V617F-mediated myelofibrosis. The expression of PRC2 target genes identified in PRC2-insufficient JAK2V617F HSPCs was not largely altered in Pcgf1-deleted JAK2V617F HSPCs. The present results revealed a tumor suppressor function for PRC1.1 in myelofibrosis and suggest that PRC1.1 insufficiency has a different impact from that of PRC2 insufficiency on the pathogenesis of myelofibrosis.

Indexed as

Cell DifferentiationMutationAnimalsFemaleJanus Kinase 2LysineMaleMiceMice, Inbred C57BLMice, KnockoutPolycomb Repressive Complex 1Primary MyelofibrosisUbiquitinationJak2 protein, mouseJanus Kinase 2LysinePcgf1 protein, mousePolycomb Repressive Complex 1

Identifiers

PMID34497325
OpenAlexW3197129731

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.