Evidence map›Paper›PMID 20424188›Full record

ArticleBlood2010

In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia.

Jaebok Choi, Julie Ritchey, Julie L Prior, Matthew Holt, William D Shannon, Elena Deych, David R Piwnica-Worms, John F DiPersio

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04482621 (Decitabine for COVID-19 Pneumonia-ARDS Treatment), which is not on this map. Cited by 189 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
189citing papers in PubMed, 4 pooled it
8.4field-weighted citation impact, top 2% 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.

NCT04482621 phase2suspendednot on this mapstarted 2020, after this paper: background citation

Decitabine for COVID-19 Pneumonia-ARDS Treatment: DART Trial

TypeinterventionalSponsorJohns Hopkins UniversityRan2020 to 2026Enrolled33ConditionsCOVID-19ArmsDecitabine, Placebo Saline
3 · Its place in the literature

Who cites it

189 citing papers in PubMed, 4 syntheses or guidelines pooled it, 306 citations in OpenAlex.

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129 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 2 countries.

Jaebok ChoiDivision of Oncology, Department of Medicine, Washington University, St Louis, MO 63110, USA.
Julie Ritchey
Julie L Prior
Matthew Holt
William D Shannon
Elena Deych
David R Piwnica-Worms
John F DiPersio
Imaging Center · USWashington University in St. Louis · US

Funding

Specimen Acquistition and Expression ProfilingP01CA101937 · NCI · WASHINGTON UNIVERSITY · PI LEY, TIMOTHY J. · 2003 to 2023
$58.8M
WU-MDACC Inter-Institutional Molecular Imaging CenterP50CA094056 · NCI · WASHINGTON UNIVERSITY · PI KOPAN, RAPHAEL · 2002 to 2016
$26.3M
Genetic Manipulation of T Cells--PreClinical ModelsR01CA083845 · NCI · WASHINGTON UNIVERSITY · PI DIPERSIO, JOHN F · 2001 to 2005
$1.6M
TARGETING THE CXCR4-SDF1 AXIS AS THERAPY FOR RELAPSED/REFRACTORY AMLR21CA132269 · NCI · WASHINGTON UNIVERSITY · PI DIPERSIO, JOHN F. · 2009 to 2010
$669k
OPTIMIZING ALLOGENEIC TRANSPLANTATION USING CXCR4 BLOCKADER21CA141523 · NCI · WASHINGTON UNIVERSITY · PI DIPERSIO, JOHN F. · 2009 to 2010
$669k
DLI using genetically modified T cells: Phase 1 trialR21CA110489 · NCI · WASHINGTON UNIVERSITY · PI DIPERSIO, JOHN F · 2004 to 2005
$627k
NCI NIH HHS CA110489NCI NIH HHS CA132269NCI NIH HHS CA141523NCI NIH HHS P01 CA101937NCI NIH HHS P50 CA094056NCI NIH HHS P50 CA94056NCI NIH HHS R01 CA083845NCI NIH HHS R01 CA83845NCI NIH HHS R21 CA110489NCI NIH HHS R21 CA132269NCI NIH HHS R21 CA141523
6 · The paper itself

Abstract

Regulatory T cells (Tregs) suppress graft-versus-host disease (GVHD) while preserving a beneficial graft-versus-leukemia (GVL) effect. Thus, their use in allogeneic stem cell transplantation (SCT) provides a promising strategy to treat GVHD. However, 3 obstacles prevent their routine use in human clinical trials: (1) low circulating number of Tregs in peripheral blood, (2) loss of suppressor function after in vitro expansion, and (3) lack of Treg-specific surface markers necessary for efficient purification. FOXP3 is exclusively expressed in Tregs and forced expression in CD4(+)CD25(-) T cells can convert these non-Tregs into Tregs with functional suppressor function. Here, we show that the FDA-approved hypomethylating agents, decitabine (Dec) and azacitidine (AzaC), induce FOXP3 expression in CD4(+)CD25(-) T cells both in vitro and in vivo. Their suppressor function is dependent on direct contact, partially dependent on perforin 1 (Prf1), but independent of granzyme B (GzmB), and surprisingly, Foxp3. Independence of Foxp3 suggests that genes responsible for the suppressor function are also regulated by DNA methylation. We have identified 48 candidate genes for future studies. Finally, AzaC treatment of mice that received a transplant of major histocompatibility complex mismatched allogeneic bone marrow and T cells mitigates GVHD while preserving GVL by peripheral conversion of alloreactive effector T cells into FOXP3(+) Tregs and epigenetic modulation of genes downstream of Foxp3 required for the suppressor function of Tregs.

Indexed as

Adoptive TransferAnimalsAzacitidineCD4-Positive T-LymphocytesCells, CulturedCombined Modality TherapyDecitabineDNA Modification MethylasesEnzyme InhibitorsFlow CytometryForkhead Transcription FactorsGene ExpressionGraft vs Host DiseaseGraft vs Leukemia EffectHumansMiceAzacitidineDecitabineDNA Modification MethylasesEnzyme InhibitorsForkhead Transcription Factors

Identifiers

PMID20424188
PMCPMC2904576
OpenAlexW2099261151

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.