Evidence map›Paper›PMID 30992567›Full record

ArticleNature chemical biology2019

CRISPR-suppressor scanning reveals a nonenzymatic role of LSD1 in AML.

Michael E Vinyard, Cindy Su, Allison P Siegenfeld, Amanda L Waterbury, Allyson M Freedy, Pallavi M Gosavi, Yongho Park, Eugene E Kwan, Benjamin D Senzer, John G Doench and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

66 citing papers in PubMed, 100 citations in OpenAlex.

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  16. Strategies that regulate LSD1 for novel therapeutics.Acta pharmaceutica Sinica. B · 2024
    Review
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  18. Article
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6 more citing papers are in PubMed but not listed here.

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

13 authors at 3 institutions in 1 country.

Michael E VinyardDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8167-1807
Cindy SuDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Allison P SiegenfeldDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8599-577X
Amanda L WaterburyDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4473-2866
Allyson M FreedyDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2953-8133
Pallavi M GosaviDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0486-5787
Yongho ParkDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3727-4545
Eugene E KwanDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Benjamin D SenzerDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
John G DoenchBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3707-9889
Daniel E BauerDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
Luca PinelloBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Brian B LiauDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA. liau@chemistry.harvard.edu.ORCID http://orcid.org/0000-0002-2985-462X
Harvard University · USBroad Institute · USBoston Children's Hospital · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

Understanding the mechanism of small molecules is a critical challenge in chemical biology and drug discovery. Medicinal chemistry is essential for elucidating drug mechanism, enabling variation of small molecule structure to gain structure-activity relationships (SARs). However, the development of complementary approaches that systematically vary target protein structure could provide equally informative SARs for investigating drug mechanism and protein function. Here we explore the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML). Through this approach, termed CRISPR-suppressor scanning, we elucidate drug mechanism of action by showing that LSD1 enzyme activity is not required for AML survival and that LSD1 inhibitors instead function by disrupting interactions between LSD1 and the transcription factor GFI1B on chromatin. Our studies clarify how LSD1 inhibitors mechanistically operate in AML and demonstrate how CRISPR-suppressor scanning can uncover novel aspects of target biology.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsEnzyme InhibitorsHistone DemethylasesHumansLeukemia, Myeloid, AcuteModels, MolecularProto-Oncogene ProteinsRepressor ProteinsSmall Molecule LibrariesEnzyme InhibitorsGFI1B protein, humanHistone DemethylasesKDM1A protein, humanProto-Oncogene ProteinsRepressor ProteinsSmall Molecule Libraries

Identifiers

PMID30992567
PMCPMC7679026
OpenAlexW2936472395

What OpenQuestion holds

Textmetadata
LicenceTDM
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.