Evidence map›Paper›PMID 30622285›Full record

ArticleLeukemia2019

JMJD1C-mediated metabolic dysregulation contributes to HOXA9-dependent leukemogenesis.

Jennifer R Lynch, Basit Salik, Patrick Connerty, Binje Vick, Halina Leung, Aster Pijning, Irmela Jeremias, Karsten Spiekermann, Toby Trahair, Tao Liu and 6 more

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.1field-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

28 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Metabolic dependencies of acute myeloid leukemia stem cells.International journal of hematology · 2024
    Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  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

16 authors at 5 institutions in 3 countries.

Jennifer R Lynch *Cancer and Stem Cell Biology Group, Children's Cancer Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Basit Salik *Cancer and Stem Cell Biology Group, Children's Cancer Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Patrick ConnertyCancer and Stem Cell Biology Group, Children's Cancer Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Binje VickGerman Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0003-1956-2778
Halina LeungCancer and Stem Cell Biology Group, Children's Cancer Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Aster PijningThe Centenary Institute, NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Camperdown, NSW 2006, Australia.
Irmela JeremiasGerman Cancer Consortium (DKTK), partner site Munich, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-1773-7677
Karsten SpiekermannGerman Cancer Research Center (DKFZ), Heidelberg, Germany.
Toby TrahairChildren's Cancer Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Tao LiuChildren's Cancer Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Michelle HaberChildren's Cancer Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Murray D NorrisChildren's Cancer Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Andrew J WooHarry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The University of Western Australia, Crawley, WA 6009, Australia.
Philip HoggThe Centenary Institute, NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Camperdown, NSW 2006, Australia.ORCID http://orcid.org/0000-0001-6486-2863
Jianlong WangDepartment of Cell, Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID http://orcid.org/0000-0002-1317-6457
Jenny Y WangCancer and Stem Cell Biology Group, Children's Cancer Institute, University of New South Wales, Sydney, NSW 2052, Australia. jwang@ccia.unsw.edu.au.
UNSW Sydney · AUGerman Cancer Research Center · DENew York Stem Cell Foundation · USThe University of Sydney · AUThe University of Western Australia · AU

Funding

Cancer Council NSW (Cancer Council New South Wales) RG15-11Department of Health | National Health and Medical Research Council (NHMRC) APP1128824
6 · The paper itself

Abstract

Abnormal metabolism is a fundamental hallmark of cancer and represents a therapeutic opportunity, yet its regulation by oncogenes remains poorly understood. Here, we uncover that JMJD1C, a jumonji C (JmjC)-containing H3K9 demethylase, is a critical regulator of aberrant metabolic processes in homeobox A9 (HOXA9)-dependent acute myeloid leukemia (AML). JMJD1C overexpression increases in vivo cell proliferation and tumorigenicity through demethylase-independent upregulation of a glycolytic and oxidative program, which sustains leukemic cell bioenergetics and contributes to an aggressive AML phenotype in vivo. Targeting JMJD1C-mediated metabolism via pharmacologic inhibition of glycolysis and oxidative phosphorylation led to ATP depletion, induced necrosis/apoptosis and decreased tumor growth in vivo in leukemias co-expressing JMJD1C and HOXA9. The anti-metabolic therapy effectively diminished AML stem/progenitor cells and reduced tumor burden in a primary AML patient-derived xenograft. Our data establish a direct link between drug responses and endogenous expression of JMJD1C and HOXA9 in human AML cell line- and patient-derived xenografts. These findings demonstrate a previously unappreciated role for JMJD1C in counteracting adverse metabolic changes and retaining the metabolic integrity during tumorigenesis, which can be exploited therapeutically.

Indexed as

Gene Expression Regulation, LeukemicGlycolysisOxidative PhosphorylationAnimalsHomeodomain ProteinsHumansJumonji Domain-Containing Histone DemethylasesLeukemia, Myeloid, AcuteMiceMice, Inbred NODMice, SCIDNeoplastic Stem CellsOxidoreductases, N-DemethylatingTumor Cells, CulturedXenograft Model Antitumor Assayshomeobox protein HOXA9Homeodomain ProteinsJMJD1C protein, humanJumonji Domain-Containing Histone DemethylasesOxidoreductases, N-Demethylating

Identifiers

PMID30622285
OpenAlexW2910700240

What OpenQuestion holds

Textmetadata
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.