Evidence map›Paper›PMID 30528456›Full record

ArticleEBioMedicine2019

Installation of a cancer promoting WNT/SIX1 signaling axis by the oncofusion protein MLL-AF9.

Li-Shu Zhang, Xunlei Kang, Jianming Lu, Yuannyu Zhang, Xiaofeng Wu, Guojin Wu, Junke Zheng, Rubina Tuladhar, Heping Shi, Qiaoling Wang and 10 more

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

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

13 citing papers in PubMed, 25 citations in OpenAlex.

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  12. Wnt Signaling in Leukemia and Its Bone Marrow Microenvironment.International journal of molecular sciences · 2020
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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

20 authors at 4 institutions in 2 countries.

Li-Shu ZhangDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Xunlei KangDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jianming LuDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Yuannyu ZhangDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Xiaofeng WuDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Guojin WuDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Junke ZhengDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Rubina TuladharDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Heping ShiDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Qiaoling WangDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Lorraine MorlockDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Huiyu YaoDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Lily Jun-Shen HuangDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Pascal MaireInstitut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS), UMR, 8104, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1016, Paris, France.
James KimDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Noelle WilliamsDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jian XuDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Chuo ChenDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cheng Cheng ZhangDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Lawrence LumDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: lawrence.lum@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USChildren's Medical Center · USCentre National de la Recherche Scientifique · FRSouthwestern Medical Center · US

Funding

UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI GIBBONS, DON LYNN · 1996 to 2024
$57.4M
Chemical disruption of Wnt-mediated signal transductionR01CA168761 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI KIM, JAMES · 2013 to 2017
$2.3M
NCI NIH HHS P50 CA070907NCI NIH HHS R01 CA168761
6 · The paper itself

Abstract

backgroundChromosomal translocation-induced expression of the chromatin modifying oncofusion protein MLL-AF9 promotes acute myelocytic leukemia (AML). Whereas WNT/β-catenin signaling has previously been shown to support MLL-AF9-driven leukemogenesis, the mechanism underlying this relationship remains unclear.

methodsWe used two novel small molecules targeting WNT signaling as well as a genetically modified mouse model that allow targeted deletion of the WNT protein chaperone Wntless (WLS) to evaluate the role of WNT signaling in AML progression. ATAC-seq and transcriptome profiling were deployed to understand the cellular consequences of disrupting a WNT signaling in leukemic initiating cells (LICs).

findingsWe identified Six1 to be a WNT-controlled target gene in MLL-AF9-transformed leukemic initiating cells (LICs). MLL-AF9 alters the accessibility of Six1 DNA to the transcriptional effector TCF7L2, a transducer of WNT/β-catenin gene expression changes. Disruption of WNT/SIX1 signaling using inhibitors of the Wnt signaling delays the development of AML.

interpretationBy rendering TCF/LEF-binding elements controlling Six1 accessible to TCF7L2, MLL-AF9 promotes WNT/β-catenin-dependent growth of LICs. Small molecules disrupting WNT/β-catenin signaling block Six1 expression thereby disrupting leukemia driven by MLL fusion proteins.

Indexed as

AnimalsHEK293 CellsHeLa CellsHL-60 CellsHomeodomain ProteinsHumansIntracellular Signaling Peptides and ProteinsLeukemia, Myeloid, AcuteMiceMyeloid-Lymphoid Leukemia ProteinNeoplasm TransplantationNeoplastic Stem CellsOncogene Proteins, FusionReceptors, G-Protein-CoupledSmall Molecule LibrariesTHP-1 CellsHomeodomain ProteinsIntracellular Signaling Peptides and ProteinsMLL-AF9 fusion protein, humanMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionReceptors, G-Protein-CoupledSIX1 protein, humanSmall Molecule LibrariesTCF7L2 protein, humanTranscription Factor 7-Like 2 ProteinWLS protein, human

Identifiers

PMID30528456
PMCPMC6354558
OpenAlexW2903758937

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.