Evidence map›Paper›PMID 32029705›Full record

ArticleBlood cancer journal2020

The RUNX1-ETO target gene RASSF2 suppresses t(8;21) AML development and regulates Rac GTPase signaling.

Samuel A Stoner, Katherine Tin Heng Liu, Elizabeth T Andrews, Mengdan Liu, Kei-Ichiro Arimoto, Ming Yan, Amanda G Davis, Stephanie Weng, Michelle Dow, Su Xian and 3 more

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

Article in Blood cancer journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 27% 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

11 citing papers in PubMed, 13 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Review
  6. [Characteristics of N6-methyladenosine modification patterns in t(8;21) acute myeloid leukemia].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022
    Article
  7. Insights from DOCK2 in cell function and pathophysiology.Frontiers in molecular biosciences · 2022
    Review
  8. Article
  9. Review
  10. Article
  11. 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 2 institutions in 1 country.

Samuel A StonerMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Katherine Tin Heng LiuMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Elizabeth T AndrewsMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Mengdan LiuMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Kei-Ichiro ArimotoMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Ming YanMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Amanda G DavisMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0003-4356-7480
Stephanie WengMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Michelle DowDivision of Medical Genetics, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Su XianDivision of Medical Genetics, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-8295-876X
Russell C DeKelverMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Hannah CarterMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Dong-Er ZhangMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA. dez@ucsd.edu.
University of California San Diego · USUniversity of California San Diego Medical Center · US

Funding

GENETIC MECHANISMS AND REGULATIONT32GM007240 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMPTON, RANDOLPH Y. · 1985 to 2019
$23.8M
San Diego Biomedical Informatics Education & Research (SABER)T15LM011271 · NLM · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHAMIM NEMATI · 2012 to 2026
$9.7M
Molecular Mechanism of Leukemogenesis Involving AML1-ETOR01CA104509 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHANG, DONG-ER · 2004 to 2025
$6.6M
Network approaches to identify cancer drivers from high-dimensional tumor dataDP5OD017937 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARTER, HANNAH KATHRYN · 2013 to 2017
$1.9M
Tumor Suppressor RASSF2 in t(8;21) Acute Myeloid LeukemiaF31CA189452 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI STONER, SAMUEL A · 2014 to 2016
$104k
NCI NIH HHS F31 CA189452NCI NIH HHS R01 CA104509NIGMS NIH HHS T32 GM007240NIH HHS DP5 OD017937NLM NIH HHS T15 LM011271
6 · The paper itself

Abstract

Large-scale chromosomal translocations are frequent oncogenic drivers in acute myeloid leukemia (AML). These translocations often occur in critical transcriptional/epigenetic regulators and contribute to malignant cell growth through alteration of normal gene expression. Despite this knowledge, the specific gene expression alterations that contribute to the development of leukemia remain incompletely understood. Here, through characterization of transcriptional regulation by the RUNX1-ETO fusion protein, we have identified Ras-association domain family member 2 (RASSF2) as a critical gene that is aberrantly transcriptionally repressed in t(8;21)-associated AML. Re-expression of RASSF2 specifically inhibits t(8;21) AML development in multiple models. Through biochemical and functional studies, we demonstrate RASSF2-mediated functions to be dependent on interaction with Hippo kinases, MST1 and MST2, but independent of canonical Hippo pathway signaling. Using proximity-based biotin labeling we define the RASSF2-proximal proteome in leukemia cells and reveal association with Rac GTPase-related proteins, including an interaction with the guanine nucleotide exchange factor, DOCK2. Importantly, RASSF2 knockdown impairs Rac GTPase activation, and RASSF2 expression is broadly correlated with Rac-mediated signal transduction in AML patients. Together, these data reveal a previously unappreciated mechanistic link between RASSF2, Hippo kinases, and Rac activity with potentially broad functional consequences in leukemia.

Indexed as

Gene Expression Regulation, NeoplasticTranslocation, GeneticAnimalsBiomarkers, TumorChromosomes, Human, Pair 21Chromosomes, Human, Pair 8HumansLeukemia, Myeloid, AcuteMiceMice, Inbred C57BLOncogene Proteins, Fusionrac GTP-Binding ProteinsRNA, Long NoncodingTumor Cells, CulturedTumor Suppressor ProteinsXenograft Model Antitumor AssaysBiomarkers, TumorOncogene Proteins, Fusionrac GTP-Binding ProteinsRASSF2 protein, humanRNA, Long NoncodingRUNX1-IT1 long non-coding RNA, humanTumor Suppressor Proteins

Identifiers

PMID32029705
PMCPMC7005177
OpenAlexW3005151264

What OpenQuestion holds

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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.