Evidence map›Paper›PMID 33507291›Full record

ArticleBlood2021

Prostaglandin E2 stimulates cAMP signaling and resensitizes human leukemia cells to glucocorticoid-induced cell death.

Justine E Roderick, Kayleigh M Gallagher, Leonard C Murphy, Kevin W O'Connor, Katherine Tang, Boyao Zhang, Michael A Brehm, Dale L Greiner, Jun Yu, Lihua Julie Zhu and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
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

12 authors at 1 institution in 1 country.

Justine E RoderickDepartment of Molecular, Cell, and Cancer Biology.
Kayleigh M GallagherDepartment of Molecular, Cell, and Cancer Biology.
Leonard C MurphyDepartment of Molecular, Cell, and Cancer Biology.
Kevin W O'ConnorDepartment of Molecular, Cell, and Cancer Biology.
Katherine TangDepartment of Medicine, and.
Boyao ZhangDepartment of Medicine, and.
Michael A BrehmProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
Dale L GreinerProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
Jun YuDepartment of Molecular, Cell, and Cancer Biology.
Lihua Julie ZhuDepartment of Molecular, Cell, and Cancer Biology.
Michael R GreenDepartment of Molecular, Cell, and Cancer Biology.
Michelle A KelliherDepartment of Molecular, Cell, and Cancer Biology.
University of Massachusetts Chan Medical School · US

Funding

University of Massachusetts Center for Clinical Science and Translational SupplementUL1TR001453 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUZURIAGA, KATHERINE F · 2015 to 2024
$39.0M
Mechanism(s) of TAL-1/SCL-mediated LeukemogenesisR01CA096899 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MICHELLE ALICE KELLIHER · 2004 to 2026
$6.9M
Rip Proteins in Innate Immune SignalingR01AI075118 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KELLIHER, MICHELLE ALICE · 2009 to 2024
$6.7M
Medical Scientist Training at UMMS Administrative SupplementT32GM107000 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KIEFE, CATARINA I. · 2013 to 2022
$4.9M
Novel humanized mouse model developed from cord blood CD34 positive HSC and autologous iPS cell derived thymusR01AI132963 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BREHM, MICHAEL ALLEN, MAEHR, RENE · 2017 to 2021
$4.4M
Translational Cancer Biology Training ProgramT32CA130807 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MERCURIO, ARTHUR M · 2008 to 2018
$2.7M
Targeting dormant leukemia-initiating cells in T-cell acute lymphoblastic leukemiaF30CA257270 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI O'CONNOR, KEVIN · 2021 to 2024
$153k
NCATS NIH HHS UL1 TR001453NCI NIH HHS F30 CA257270NCI NIH HHS R01 CA096899NCI NIH HHS T32 CA130807NIAID NIH HHS R01 AI075118NIAID NIH HHS R01 AI132963NIGMS NIH HHS T32 GM107000
6 · The paper itself

Abstract

Glucocorticoid (GC) resistance remains a clinical challenge in pediatric acute lymphoblastic leukemia where response to GC is a reliable prognostic indicator. To identify GC resistance pathways, we conducted a genome-wide, survival-based, short hairpin RNA screen in murine T-cell acute lymphoblastic leukemia (T-ALL) cells. Genes identified in the screen interfere with cyclic adenosine monophosphate (cAMP) signaling and are underexpressed in GC-resistant or relapsed ALL patients. Silencing of the cAMP-activating Gnas gene interfered with GC-induced gene expression, resulting in dexamethasone resistance in vitro and in vivo. We demonstrate that cAMP signaling synergizes with dexamethasone to enhance cell death in GC-resistant human T-ALL cells. We find the E prostanoid receptor 4 expressed in T-ALL samples and demonstrate that prostaglandin E2 (PGE2) increases intracellular cAMP, potentiates GC-induced gene expression, and sensitizes human T-ALL samples to dexamethasone in vitro and in vivo. These findings identify PGE2 as a target for GC resensitization in relapsed pediatric T-ALL.

Indexed as

1-Methyl-3-isobutylxanthineAnimalsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorChildChromograninsColforsinCyclic AMPDexamethasoneDinoprostoneDrug Resistance, NeoplasmFemaleGene Expression Regulation, LeukemicGTP-Binding Protein alpha Subunits, GsHumansMale1-Methyl-3-isobutylxanthineChromograninsColforsinCyclic AMPDexamethasoneDinoprostoneGNAS protein, humanGnas protein, mouseGTP-Binding Protein alpha Subunits, GsNeoplasm ProteinsNR3C1 protein, humanNR3C1 protein, mouseReceptors, GlucocorticoidReceptors, Prostaglandin E, EP4 SubtypeRNA, Small Interfering

Identifiers

PMID33507291
PMCPMC7845005
OpenAlexW3047512109

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.