Evidence map›Paper›PMID 27462455›Full record

ArticleCell discovery2016

MLL1 and MLL1 fusion proteins have distinct functions in regulating leukemic transcription program.

Jing Xu, Li Li, Jie Xiong, Aaron denDekker, Andrew Ye, Hacer Karatas, Liu Liu, He Wang, Zhaohui S Qin, Shaomeng Wang and 1 more

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

Article in Cell discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

34 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. The Molecular and Biological Function of MEF2D in Leukemia.Advances in experimental medicine and biology · 2024
    Review
  11. Review
  12. An enhancer RNA recruits MLL1 to regulate transcription ofbioRxiv : the preprint server for biology · 2023
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Gene Transcription as a Therapeutic Target in Leukemia.International journal of molecular sciences · 2021
    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

11 authors at 3 institutions in 2 countries.

Jing XuDepartment of Pathology, University of Michigan , Ann Arbor, MI, USA.
Li LiDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University , Atlanta, GA, USA.
Jie XiongDepartment of Pathology, University of Michigan , Ann Arbor, MI, USA.
Aaron denDekkerDepartment of Pathology, University of Michigan , Ann Arbor, MI, USA.
Andrew YeDepartment of Pathology, University of Michigan , Ann Arbor, MI, USA.
Hacer KaratasDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Liu LiuDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
He WangChina Novartis Institutes for BioMedical Research , Shanghai, China.
Zhaohui S QinDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University , Atlanta, GA, USA.
Shaomeng WangDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Yali DouDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
University of Michigan–Ann Arbor · USEmory University · USNovartis (China) · CN

Funding

Lung Immunopathology Training Stipend SupplementT32HL007517 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUKACS, NICHOLAS W · 1985 to 2022
$6.1M
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
NCI NIH HHS R01 CA177307NHLBI NIH HHS T32 HL007517NIGMS NIH HHS R01 GM082856
6 · The paper itself

Abstract

Mixed lineage leukemia protein-1 (MLL1) has a critical role in human MLL1 rearranged leukemia (MLLr) and is a validated therapeutic target. However, its role in regulating global gene expression in MLLr cells, as well as its interplay with MLL1 fusion proteins remains unclear. Here we show that despite shared DNA-binding and cofactor interacting domains at the N terminus, MLL1 and MLL-AF9 are recruited to distinct chromatin regions and have divergent functions in regulating the leukemic transcription program. We demonstrate that MLL1, probably through C-terminal interaction with WDR5, is recruited to regulatory enhancers that are enriched for binding sites of E-twenty-six (ETS) family transcription factors, whereas MLL-AF9 binds to chromatin regions that have no H3K4me1 enrichment. Transcriptome-wide changes induced by different small molecule inhibitors also highlight the distinct functions of MLL1 and MLL-AF9. Taken together, our studies provide novel insights on how MLL1 and MLL fusion proteins contribute to leukemic gene expression, which have implications for developing effective therapies in the future.

Indexed as

acute myeloid leukemiaepigenetic therapeuticsmeninMLL1MLL fusion proteins

Identifiers

PMID27462455
PMCPMC4869169
OpenAlexW2406490019

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.