Evidence map›Paper›PMID 26728554›Full record

ArticleGenes & development2016

Acute myeloid leukemia requires Hhex to enable PRC2-mediated epigenetic repression of Cdkn2a.

Benjamin J Shields, Jacob T Jackson, Donald Metcalf, Wei Shi, Qiutong Huang, Alexandra L Garnham, Stefan P Glaser, Dominik Beck, John E Pimanda, Clifford W Bogue and 3 more

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

Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
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  6. Article
  7. Review
  8. Article
  9. Transcriptional regulation of INK4/ARF locus by cis and trans mechanisms.Frontiers in cell and developmental biology · 2022
    Review
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  18. RUNX1 cooperates with FLT3-ITD to induce leukemia.The Journal of experimental medicine · 2017
    Article
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  20. 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

13 authors at 4 institutions in 2 countries.

Benjamin J ShieldsCancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia;
Jacob T JacksonCancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia;
Donald MetcalfCancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia;
Wei ShiBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia; Computing and Information Systems, University of Melbourne, Parkville, Victoria 3050, Australia;
Qiutong HuangCancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia;
Alexandra L GarnhamBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia;
Stefan P GlaserCancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia;
Dominik BeckLowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia;
John E PimandaLowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia;
Clifford W BogueYale University School of Medicine, New Haven, Connecticut 06510, USA;
Gordon K SmythDepartment of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia; Mathematics and Statistics, University of Melbourne, Parkville, Victoria 3050, Australia.
Warren S AlexanderCancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia;
Matthew P McCormackCancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia;
University of Melbourne · AUWalter and Eliza Hall Institute of Medical Research · AUUNSW Sydney · AUYale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Unlike clustered HOX genes, the role of nonclustered homeobox gene family members in hematopoiesis and leukemogenesis has not been extensively studied. Here we found that the hematopoietically expressed homeobox gene Hhex is overexpressed in acute myeloid leukemia (AML) and is essential for the initiation and propagation of MLL-ENL-induced AML but dispensable for normal myelopoiesis, indicating a specific requirement for Hhex for leukemic growth. Loss of Hhex leads to expression of the Cdkn2a-encoded tumor suppressors p16(INK4a) and p19(ARF), which are required for growth arrest and myeloid differentiation following Hhex deletion. Mechanistically, we show that Hhex binds to the Cdkn2a locus and directly interacts with the Polycomb-repressive complex 2 (PRC2) to enable H3K27me3-mediated epigenetic repression. Thus, Hhex is a potential therapeutic target that is specifically required for AML stem cells to repress tumor suppressor pathways and enable continued self-renewal.

Indexed as

Epigenesis, GeneticAnimalsCell Line, TumorCyclin-Dependent Kinase Inhibitor p16Gene DeletionGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansLeukemia, Myeloid, AcuteMiceMice, Inbred C57BLPolycomb Repressive Complex 2Protein BindingTranscription FactorsCyclin-Dependent Kinase Inhibitor p16Hhex protein, mouseHomeodomain ProteinsPolycomb Repressive Complex 2Transcription Factorsacute myeloid leukemiahomeoboxself-renewaltranscription factortumor suppressor

Identifiers

PMID26728554
PMCPMC4701980
OpenAlexW2229011368

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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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.