Evidence map›Paper›PMID 25822018›Full record

Trial reportThe Journal of clinical investigation2015

Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia.

Kristen Meldi, Tingting Qin, Francesca Buchi, Nathalie Droin, Jason Sotzen, Jean-Baptiste Micol, Dorothée Selimoglu-Buet, Erico Masala, Bernardino Allione, Daniela Gioia and 6 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical TrialMulticenter Study
In one paragraph

Trial report in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
17.3field-weighted citation impact, top 1% 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.

NCT03217903 naunknown statusnot on this mapstarted 2017, after this paper: background citation

High Risk Myelodysplasia Treated by Azacytidine : Genetic and Epigenetic (MYRAGE)

TypeinterventionalSponsorCentral Hospital, Nancy, FranceRan2017 to 2022Enrolled32ConditionsHigh-risk Myelodysplastic Syndromes With Excess BlastsArmsMyelogram
NCT04806906 phase2completednot on this mapstarted 2021, after this paper: background citation

A Phase 2, Monocentric, Pilot Study to Evaluate Safety and Efficacy of CC 486 (Oral Azacitidine) Plus Best Supportive Care as Maintenance of Response to sc Azacitidine in IPSS Higher Risk Elderly MDS Patients

TypeinterventionalSponsorUniversity of FlorenceRan2021 to 2025Enrolled11ConditionsMDS, CMMLArmsCC-486
3 · Its place in the literature

Who cites it

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.

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32 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

16 authors at 9 institutions in 3 countries.

Kristen Meldi
Tingting Qin
Francesca Buchi
Nathalie Droin
Jason Sotzen
Jean-Baptiste Micol
Dorothée Selimoglu-Buet
Erico Masala
Bernardino Allione
Daniela Gioia
Antonella Poloni
Monia Lunghi
Eric Solary
Omar Abdel-Wahab
Valeria Santini
Maria E Figueroa
University of Michigan–Ann Arbor · USInserm · FRInstitut Gustave Roussy · FRItalian Foundation of Myelodysplastic Syndromes · ITUniversity of Florence · ITAzienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo · ITAzienda Ospedaliero-Universitaria Careggi · ITMemorial Sloan Kettering Cancer Center · USUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · IT

Funding

Training Program in Tumor MicroenvironmentT32CA009676 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, Analisa Virginia DiFeo · 1992 to 2026
$7.3M
Role of ASXL1 mutations in myeloid malignanciesK08CA160647 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR · 2011 to 2015
$849k
NCI NIH HHS 1K08CA160647-01NCI NIH HHS K08 CA160647NCI NIH HHS T32 CA009676NCI NIH HHS T32 CA 9676-22
6 · The paper itself

Abstract

Myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in genes encoding epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable, with few means to predict which patients will benefit. Here, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients who were responsive or resistant to decitabine (DAC) in order to develop a molecular means of predicting response at diagnosis. While somatic mutations did not differentiate responders from nonresponders, we identified 167 differentially methylated regions (DMRs) of DNA at baseline that distinguished responders from nonresponders using next-generation sequencing. These DMRs were primarily localized to nonpromoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. Transcriptional analysis revealed differences in gene expression at diagnosis between responders and nonresponders. In responders, the upregulated genes included those that are associated with the cell cycle, potentially contributing to effective DAC incorporation. Treatment with CXCL4 and CXCL7, which were overexpressed in nonresponders, blocked DAC effects in isolated normal CD34+ and primary CMML cells, suggesting that their upregulation contributes to primary DAC resistance.

Indexed as

Gene Expression ProfilingGenes, NeoplasmAgedAged, 80 and overAntimetabolites, AntineoplasticAzacitidinebeta-ThromboglobulinBone MarrowDecitabineDNA, IntergenicDNA MethylationDNA Mutational AnalysisDrug Resistance, NeoplasmEnhancer Elements, GeneticFemaleGene Expression Regulation, NeoplasticAntimetabolites, AntineoplasticAzacitidinebeta-ThromboglobulinDecitabineDNA, IntergenicNeoplasm ProteinsPlatelet Factor 4PPBP protein, human

Identifiers

PMID25822018
PMCPMC4611703
OpenAlexW1998931089

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.