Evidence map›Paper›PMID 37353528›Full record

ArticleCell death & disease2023

Mdm2/p53 levels in bone marrow mesenchymal stromal cells are essential for maintaining the hematopoietic niche in response to DNA damage.

Rasoul Pourebrahim, Rafael Heinz Montoya, Zoe Alaniz, Lauren Ostermann, Patrick P Lin, Bin Liu, Edward Ayoub, Jared K Burks, Michael Andreeff

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

Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.5field-weighted citation impact, top 16% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Rasoul Pourebrahim *Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0003-1175-2032
Rafael Heinz Montoya *Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zoe AlanizSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lauren OstermannSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-3330-2174
Patrick P LinDepartment of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bin LiuDepartment of Epigenetic and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Edward AyoubSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jared K BurksSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael AndreeffSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. mandreef@mdanderson.org.ORCID 0000-0002-1144-1958
The University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Single Cell Spatial Analysis in TissueR50CA243707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BURKS, JARED KYLE · 2020 to 2024
$1.3M
Targeting Quiescence Pathways to Overcome Chemoresistance in EVI1-Overexpressing LeukemiaF32CA271697 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AYOUB, EDWARD · 2022 to 2024
$226k
NCI NIH HHS F32 CA271697NCI NIH HHS P30 CA016672NCI NIH HHS R50 CA243707
6 · The paper itself

Abstract

Mesenchymal stromal cells (MSCs) are a key component of the bone marrow (BM) niche, providing essential support required for the maintenance of hematopoietic stem cells. To advance our understanding of physiological functions of p53 and Mdm2 in BM-MSCs, we developed traceable conditional mouse models targeting Mdm2 and/or Trp53 in vivo. We demonstrate that Mdm2 is essential for the emergence, maintenance, and hematopoietic support of BM-MSCs. Mdm2 haploinsufficiency in BM-MSCs resulted in genotoxic stress-associated thrombocytopenia, suggesting a functional role for Mdm2 in hematopoiesis. In a syngeneic mouse model of acute myeloid leukemia (AML), Trp53 deletion in BM-MSCs improved survival, and protected BM against hematopoietic toxicity from a murine Mdm2i, DS-5272. The transcriptional changes were associated with dysregulation of glycolysis, gluconeogenesis, and Hif-1α in BM-MSCs. Our results reveal a physiologic function of Mdm2 in BM-MSC, identify a previously unknown role of p53 pathway in BM-MSC-mediated support in AML and expand our understanding of the mechanism of hematopoietic toxicity of MDM2is.

Indexed as

Mesenchymal Stem CellsProto-Oncogene Proteins c-mdm2ThrombocytopeniaTumor Suppressor Protein p53AnimalsBone MarrowBone Marrow CellsDisease Models, AnimalDNA DamageMiceMdm2 protein, mouseProto-Oncogene Proteins c-mdm2Trp53 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID37353528
PMCPMC10290070
OpenAlexW4381804851

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.