Evidence map›Paper›PMID 30171262›Full record

ArticleOncogene2019

Hedgehog/GLI1 activation leads to leukemic transformation of myelodysplastic syndrome in vivo and GLI1 inhibition results in antitumor activity.

Bonnie W Lau, Kyounghee Huh, Rafael Madero-Marroquin, Federico De Marchi, Yiting Lim, Qiuju Wang, Francisco Lobo, Luigi Marchionni, Douglas B Smith, Amy DeZern and 4 more

Abstract read
In one paragraph

Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

19 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. High GLI-1 Expression is a Reliable Indicator of Bad Prognosis in Newly Diagnosed Acute Leukemia Patients.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023
    Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Emerging Therapies for the Myelodysplastic Syndromes.Clinical hematology international · 2020
    Review
  18. Review
  19. 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

14 authors at 4 institutions in 2 countries.

Bonnie W LauThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Kyounghee HuhThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Rafael Madero-MarroquinThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Federico De MarchiThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Yiting LimThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Qiuju WangThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Francisco LoboThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Luigi MarchionniThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Douglas B SmithThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Amy DeZernThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Mark J LevisThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Peter D AplanGenetics Branch National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
William MatsuiLIVESTRONG Cancer Institutes, Dell Medical School, The University of Texas at Austin, Austin, TX, 78712USA, USA. matsuwi@jhmi.edu.
Lukasz P GondekThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. lgondek1@jhmi.edu.
Johns Hopkins University · USSidney Kimmel Comprehensive Cancer Center · USNational Institutes of Health · USThe University of Texas at Austin · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
Pre-clinical Studies of Therapy for Myelodysplastic SyndromeZIABC010983 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI APLAN, PETER · 2009 to 2025
$8.2M
MENTORING AND RESEARCH IN CANCER STEM CELLSK24CA198315 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI MATSUI, WILLIAM H · 2016 to 2020
$933k
Hedgehog Signaling in the Progression of Myelodysplastic SyndromesK08HL136894 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI GONDEK, LUKASZ PAWEL · 2017 to 2021
$859k
NCI NIH HHS K24 CA198315NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA023108NHLBI NIH HHS K08 HL136894
6 · The paper itself

Abstract

Myelodysplastic syndromes (MDSs) are stem cell disorders with risk of transformation to acute myeloid leukemia (AML). Gene expression profiling reveals transcriptional expression of GLI1, of Hedgehog (Hh) signaling, in poor-risk MDS/AML. Using a murine model of MDS we demonstrated that constitutive Hh/Gli1 activation accelerated leukemic transformation and decreased overall survival. Hh/Gli1 activation resulted in clonal expansion of phenotypically defined granulocyte macrophage progenitors (GMPs) and acquisition of self-renewal potential in a non-self-renewing progenitor compartment. Transcriptome analysis of GMPs revealed enrichment in gene signatures of self-renewal pathways, operating via direct Gli1 activation. Using human cell lines we demonstrated that in addition to canonical Hh signaling, GLI1 is activated in a Smoothened-independent manner. GLI1 knockdown or inhibition with GANT61 resulted in decreased proliferation and clonogenic potential. Our data suggest that GLI1 activation is frequent in MDS during disease progression and inhibition of GLI1 is an attractive therapeutic target for a subset of patients.

Indexed as

Cell Line, TumorCell ProliferationCell Transformation, NeoplasticGranulocyte-Macrophage Progenitor CellsHedgehog ProteinsHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesPyridinesPyrimidinesZinc Finger Protein GLI1GANT 61GLI1 protein, humanHedgehog ProteinsPyridinesPyrimidinesZinc Finger Protein GLI1

Identifiers

PMID30171262
PMCPMC6358463
OpenAlexW2889410066

What OpenQuestion holds

Textmetadata
LicenceTDM
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.