Evidence map›Paper›PMID 35034955›Full record

ArticleLeukemia2022

Inhibition of the deubiquitinating enzyme USP47 as a novel targeted therapy for hematologic malignancies expressing mutant EZH2.

Jing Yang, Ellen L Weisberg, Shuang Qi, Wei Ni, Husheng Mei, Zuowei Wang, Chengcheng Meng, Shengzhe Zhang, Mingqi Hou, Ziping Qi and 12 more

Abstract read
PubMed Publisher
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 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

9 citing papers in PubMed, 19 citations in OpenAlex.

  1. Targeting DESI2 as a Novel Therapeutic Strategy for JAK2-Mutant Leukemias.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

22 authors at 3 institutions in 2 countries.

Jing Yang *Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.ORCID http://orcid.org/0000-0001-6441-709X
Ellen L Weisberg *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5679-9531
Shuang Qi *Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Wei NiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5729-827X
Husheng MeiAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Zuowei WangAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Chengcheng MengDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Shengzhe ZhangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Mingqi HouAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Ziping QiAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Aoli WangAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Yunyun JiangAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Zongru JiangAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Tao HuangAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Qingwang LiuAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Robert S MaginDepartment of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Laura DohertyDepartment of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Wenchao WangAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.
Jing LiuAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China.ORCID http://orcid.org/0000-0001-9513-3591
Sara J BuhrlageDepartment of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. saraj_buhrlage@dfci.harvard.edu.ORCID http://orcid.org/0000-0003-4562-1823
Qingsong LiuAnhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China. qsliu97@hmfl.ac.cn.ORCID http://orcid.org/0000-0002-7829-2547
James D GriffinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. james_griffin@dfci.harvard.edu.ORCID http://orcid.org/0000-0003-1823-7930
Harvard University · USChinese Academy of Sciences · CNUniversity of Science and Technology of China · CN

Funding

Targeting SYK Kinase in AMLP50CA206963 · NCI · DANA-FARBER CANCER INST · PI STEGMAIER, KIMBERLY · 2017 to 2021
$10.6M
NCI NIH HHS P50 CA206963
6 · The paper itself

Abstract

Activating mutations in EZH2, the catalytic component of PRC2, promote cell proliferation, tumorigenesis, and metastasis through enzymatic or non-enzymatic activity. The EZH2-Y641 gain-of-function mutation is one of the most significant in diffuse large B-cell lymphoma (DLBCL). Although EZH2 kinase inhibitors, such as EPZ-6438, provide clinical benefit, certain cancer cells are resistant to the enzymatic inhibition of EZH2 because of the inability to functionally target mutant EZH2, or because of cells' dependence on the non-histone methyltransferase activity of EZH2. Consequently, destroying mutant EZH2 protein may be more effective in targeting EZH2 mutant cancers that are dependent on the non-catalytic activity of EZH2. Here, using extensive selectivity profiling, combined with genetic and animal model studies, we identified USP47 as a novel regulator of mutant EZH2. Inhibition of USP47 would be anticipated to block the function of mutated EZH2 through induction of EZH2 degradation by promoting its ubiquitination. Moreover, targeting of USP47 leads to death of mutant EZH2-positive cells in vitro and in vivo. Taken together, we propose targeting USP47 with a small molecule inhibitor as a novel potential therapy for DLBCL and other hematologic malignancies characterized by mutant EZH2 expression.

Indexed as

Hematologic NeoplasmsHistonesAnimalsCell Line, TumorDeubiquitinating EnzymesEnhancer of Zeste Homolog 2 ProteinGene Expression Regulation, NeoplasticHumansMethylationPolycomb Repressive Complex 2Deubiquitinating EnzymesEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistonesPolycomb Repressive Complex 2

Identifiers

PMID35034955
OpenAlexW4205987228

What OpenQuestion 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 OpenQuestion graph.