Evidence map›Paper›PMID 25348669›Full record

ArticleClinical chemistry2015

Validation of DNA methylation to predict outcome in acute myeloid leukemia by use of xMELP.

Gerald B W Wertheim, Catherine Smith, Marlise Luskin, Alison Rager, Maria E Figueroa, Martin Carroll, Stephen R Master

Open access · bronzeAbstract read
In one paragraph

Article in Clinical chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

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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

7 authors at 4 institutions in 1 country.

Gerald B W WertheimDepartment of Pathology, Children's Hospital of Philadelphia; Department of Pathology and Laboratory Medicine.
Catherine SmithDepartment of Pathology, Children's Hospital of Philadelphia;
Marlise LuskinDivision of Hematology and Oncology, and.
Alison RagerDivision of Hematology and Oncology, and.
Maria E FigueroaDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI.
Martin CarrollDivision of Hematology and Oncology, and Abramson Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
Stephen R MasterDepartment of Pathology and Laboratory Medicine, srmaster@mail.med.upenn.edu.
Children's Hospital of Philadelphia · USPalmetto Hematology Oncology · USUniversity of Michigan–Ann Arbor · USUniversity of Pennsylvania · US

Funding

INSTITUTIONAL CLINICAL AND TRANSLATIONAL SCIENCE AWARDUL1RR024134 · NCRR · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2006 to 2011
$70.4M
Institutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9M
Stem Cells, Differentiation and Therapeutic Resistance in AMLR01CA149566 · NCI · UNIVERSITY OF PENNSYLVANIA · PI CARROLL, MARTIN · 2011 to 2015
$3.0M
(PDQ5)Integrated Genetic and Epigenetic Prognostication for Acute Myeloid LeukemiR21CA185365 · NCI · UNIVERSITY OF PENNSYLVANIA · PI CARROLL, MARTIN · 2014 to 2015
$383k
Therapeutic targeting of Src kinase signal transduction pathways in AMLI01BX000918 · VA · PHILADELPHIA VA MEDICAL CENTER · PI CARROLL, MARTIN · 2012 to 2015
–
BLRD VA I01 BX000918NCATS NIH HHS UL1 TR000003NCATS NIH HHS UL1TR000003NCI NIH HHS 1R01CA149566-01A1NCI NIH HHS 1R21CA185365-01NCI NIH HHS 5R21CA185365-02NCI NIH HHS R01 CA149566NCI NIH HHS R21 CA185365NCRR NIH HHS UL1RR024134
6 · The paper itself

Abstract

backgroundEpigenetic dysregulation involving alterations in DNA methylation is a hallmark of various types of cancer, including acute myeloid leukemia (AML). Although specific cancer types and clinical aggressiveness of tumors can be determined by DNA methylation status, the assessment of DNA methylation at multiple loci is not routinely performed in the clinical laboratory.

methodsWe recently described a novel microsphere-based assay for multiplex evaluation of DNA methylation. In the current study, we validated and used an improved assay [termed expedited microsphere HpaII small fragment Enrichment by Ligation-mediated PCR (xMELP)] that can be performed with appropriate clinical turnaround time.

resultsUsing the xMELP assay in conjunction with a new 17-locus random forest classifier that has been trained using 344 AML samples, we were able to segregate an independent cohort of 70 primary AML patients into methylation-determined subgroups with significantly distinct mortality risk (P = 0.009). We also evaluated precision, QC parameters, and preanalytic variables of the xMELP assay and determined the sensitivity of the random forest classifier score to failure at 1 or more loci.

conclusionsOur results demonstrate that xMELP performance is suitable for implementation in the clinical laboratory and predicts AML outcome in an independent patient cohort.

Indexed as

Epigenesis, GeneticCohort StudiesDisease-Free SurvivalDNADNA MethylationHumansKaplan-Meier EstimateLeukemia, Myeloid, AcuteMultivariate AnalysisPolymerase Chain ReactionPrognosisReproducibility of ResultsDNA

Identifiers

PMID25348669
PMCPMC4384518
OpenAlexW2113371054

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.