Evidence map›Paper›PMID 24389101›Full record

ArticleMolecular cell2014

Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia.

Fang Cao, Elizabeth C Townsend, Hacer Karatas, Jing Xu, Li Li, Shirley Lee, Liu Liu, Yong Chen, Peter Ouillette, Jidong Zhu and 7 more

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

Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed
15.1field-weighted citation impact, top 1% 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

191 citing papers in PubMed, 297 citations in OpenAlex.

  1. Article
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  9. Review
  10. ZMYND11 Restrains KMT2A to Enable a Neuronal Developmental Program.bioRxiv : the preprint server for biology · 2025
    Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Lysine and arginine methylation of transcription factors.Cellular and molecular life sciences : CMLS · 2024
    Review
  19. Article
  20. Article

131 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

17 authors at 7 institutions in 2 countries.

Fang CaoDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Elizabeth C TownsendDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Hacer KaratasDepartment of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Jing XuDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Li LiDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Shirley LeeDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Liu LiuDepartment of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Yong ChenNational Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Peter OuilletteDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Jidong ZhuInterdisciplinary Research Center of Biology and Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Jay L HessIndiana University School of Medicine, Indianapolis, IN 46202-3082, USA.
Peter AtadjaNovartis Institutes for BioMedical Research, Shanghai Novartis Research Inc., Shanghai 201203, China.
Ming LeiNational Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Zhaohui S QinDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Sami MalekDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Shaomeng WangDepartment of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: shaomeng@umich.edu.
Yali DouDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: yalid@umich.edu.
University of Michigan–Ann Arbor · USMichigan Center for Translational Pathology · USEmory University · USChinese Academy of Sciences · CNIndiana University School of MedicineNovartis (China) · CNShanghai Institutes for Biological Sciences · CN

Funding

Function of MLL in transcription regulationR01GM082856 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DOU, YALI · 2009 to 2023
$4.0M
Targeting the MLL-WDR5 protein-protein interactionR01CA177307 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DOU, YALI, WANG, SHAOMENG · 2013 to 2016
$1.8M
New Therapeutic Targets in AMLR01CA151425 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HESS, JAY L. · 2011 to 2015
$1.7M
Model-Based Methods for Analyzing ChIP Sequencing DataR01HG005119 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI QIN, ZHAOHUI · 2009 to 2012
$1.2M
Howard Hughes Medical InstituteNCI NIH HHS CA177307NCI NIH HHS R01 CA151425NCI NIH HHS R01 CA177307NHGRI NIH HHS HG005119NIGMS NIH HHS GM082856NIGMS NIH HHS R01 GM082856
6 · The paper itself

Abstract

Here we report a comprehensive characterization of our recently developed inhibitor MM-401 that targets the MLL1 H3K4 methyltransferase activity. MM-401 is able to specifically inhibit MLL1 activity by blocking MLL1-WDR5 interaction and thus the complex assembly. This targeting strategy does not affect other mixed-lineage leukemia (MLL) family histone methyltransferases (HMTs), revealing a unique regulatory feature for the MLL1 complex. Using MM-401 and its enantiomer control MM-NC-401, we show that inhibiting MLL1 methyltransferase activity specifically blocks proliferation of MLL cells by inducing cell-cycle arrest, apoptosis, and myeloid differentiation without general toxicity to normal bone marrow cells or non-MLL cells. More importantly, transcriptome analyses show that MM-401 induces changes in gene expression similar to those of MLL1 deletion, supporting a predominant role of MLL1 activity in regulating MLL1-dependent leukemia transcription program. We envision broad applications for MM-401 in basic and translational research.

Indexed as

AnimalsApoptosisCell Cycle CheckpointsCell DifferentiationCell Line, TumorCell ProliferationHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHistonesHumansIntracellular Signaling Peptides and ProteinsLeukemia, Biphenotypic, AcuteMiceMyeloid-Lymphoid Leukemia ProteinOligopeptidesProteinsHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHistonesIntracellular Signaling Peptides and ProteinsKmt2a protein, mouseMM-401Myeloid-Lymphoid Leukemia ProteinOligopeptidesProteinsProto-Oncogene Proteins c-bcl-2Wdr5 protein, mouse

Identifiers

PMID24389101
PMCPMC3965208
OpenAlexW2099984271

What OpenQuestion holds

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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.