Evidence map›Paper›PMID 38394203›Full record

ArticleScience advances2024

Therapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery.

Anthony K N Chan, Li Han, Christopher D Delaney, Xueer Wang, Elizaveta Mukhaleva, Mingli Li, Lu Yang, Sheela Pangeni Pokharel, Nicole Mattson, Michelle Garcia and 19 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
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  10. Ribosome-directed cancer therapies: the tip of the iceberg?Trends in pharmacological sciences · 2025
    Review
  11. Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  12. 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

29 authors at 5 institutions in 2 countries.

Anthony K N ChanDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0002-7091-1294
Li HanDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0002-3654-171X
Christopher D DelaneyDuke University School of Medicine, Durham, NC, USA.ORCID 0000-0002-4549-6869
Xueer WangDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0001-8771-6025
Elizaveta MukhalevaDepartment of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0002-9911-7625
Mingli LiDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0001-6921-3651
Lu YangDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0001-7952-0399
Sheela Pangeni PokharelDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Nicole MattsonDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0001-5881-3387
Michelle GarciaDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0009-0004-9927-4622
Bintao WangDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Xiaobao XuDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Leisi ZhangDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Priyanka SinghDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0002-5288-2290
Zeinab ElsayedDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0009-0009-3202-5601
Renee ChenDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Benjamin KuangDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0002-0944-0753
Jinhui WangCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.ORCID 0000-0002-3499-4336
Yate-Ching YuanDepartment of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0002-3698-9784
Bryan ChenDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Lai N ChanCenter of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Steven T RosenCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.
David HorneCity of Hope Comprehensive Cancer Center, Duarte, CA, USA.ORCID 0000-0002-9300-1082
Markus MüschenCenter of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0002-6064-8613
Jianjun ChenDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0003-3749-2902
Nagarajan VaidehiDepartment of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0001-8100-8132
Scott A ArmstrongDepartment of Pediatrics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9099-4728
Rui SuDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0002-4807-6229
Chun-Wei ChenDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.ORCID 0000-0002-8737-6830
City of Hope · USCity Of Hope National Medical Center · USHarvard University · USYale Cancer Center · USDartmouth College · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI John Charles Williams · 1985 to 2026
$86.3M
TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
Targeting SYK Kinase in AMLP50CA206963 · NCI · DANA-FARBER CANCER INST · PI GRAUBERT, TIMOTHY A · 2017 to 2021
$10.6M
Project 4U54CA243124 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI MULLIGHAN, CHARLES G. · 2019 to 2023
$10.5M
Structural dynamics underlying GPCR-G protein selectivityR01GM117923 · NIGMS · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI VAIDEHI, NAGARAJAN · 2017 to 2024
$3.8M
Targeting p38 gamma signaling to advance Cutaneous T Cell Lymphoma TherapyR01CA233922 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI ROSEN, STEVEN TERRY · 2019 to 2023
$3.4M
The role and therapeutic potential of IGF2BP2 in MLL-rearranged leukemiaR01CA271497 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Jianjun Chen · 2022 to 2026
$2.8M
Targeting FTO to treat acute myeloid leukemiaR01CA243386 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, JIANJUN · 2020 to 2024
$2.8M
Combinational Targeting the Feed-forward Epigenetic Circuitry in Mixed Lineage LeukemiaR37CA233691 · NCI · MAYO CLINIC ROCHESTER · PI CHEN, CHUN-WEI DAVID · 2019 to 2025
$2.8M
TET2-mediated epitranscriptomic regulation in leukemia microenvironmentR01CA280389 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Jianjun Chen · 2023 to 2026
$2.7M
The role and mechanism of METTL3/METTL14-mediated RNA modification in the pathogenesis and drug-resistance of AMLR01CA236399 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, JIANJUN · 2019 to 2023
$2.3M
Role of BAZ2A in MLL-r leukemia and therapeutic responseR01CA236626 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, CHUN-WEI DAVID · 2019 to 2023
$2.2M
NCI NIH HHS P01 CA066996NCI NIH HHS P30 CA033572NCI NIH HHS P50 CA206963NCI NIH HHS R00 CA197498NCI NIH HHS R01 CA214965NCI NIH HHS R01 CA233922NCI NIH HHS R01 CA236399NCI NIH HHS R01 CA236626NCI NIH HHS R01 CA243386NCI NIH HHS R01 CA259273NCI NIH HHS R01 CA271497NCI NIH HHS R01 CA278050NCI NIH HHS R01 CA280389NCI NIH HHS R37 CA233691NCI NIH HHS U54 CA243124NIGMS NIH HHS R01 GM117923
6 · The paper itself

Abstract

Epigenetic dysregulation has been reported in multiple cancers including leukemias. Nonetheless, the roles of the epigenetic reader Tudor domains in leukemia progression and therapy remain unexplored. Here, we conducted a Tudor domain-focused CRISPR screen and identified SGF29, a component of SAGA/ATAC acetyltransferase complexes, as a crucial factor for H3K9 acetylation, ribosomal gene expression, and leukemogenesis. To facilitate drug development, we integrated the CRISPR tiling scan with compound docking and molecular dynamics simulation, presenting a generally applicable strategy called CRISPR-Scan Assisted Drug Discovery (CRISPR-SADD). Using this approach, we identified a lead inhibitor that selectively targets SGF29's Tudor domain and demonstrates efficacy against leukemia. Furthermore, we propose that the structural genetics approach used in our study can be widely applied to diverse fields for de novo drug discovery.

Indexed as

LeukemiaTudor DomainAcetyltransferasesClustered Regularly Interspaced Short Palindromic RepeatsDrug DiscoveryHumansAcetyltransferases

Identifiers

PMID38394203
PMCPMC10889360
OpenAlexW4392094103

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Registered trials

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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.