Evidence map›Paper›PMID 31673932›Full record

ArticleMolecular diagnosis & therapy2019

Clinical Validation and Implementation of a Measurable Residual Disease Assay for NPM1 in Acute Myeloid Leukemia by Error-Corrected Next-Generation Sequencing.

Lauren L Ritterhouse, Megan Parilla, Chao Jie Zhen, Michelle N Wurst, Rutika Puranik, Candace M Henderson, Neda Z Joudeh, Madeline J Hartley, Rishikesh Haridas, Pankhuri Wanjari and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular diagnosis & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Review
  4. EJHaem · 2022
    Article
  5. Article
  6. Review
  7. Article
  8. NPM1 Biology in Myeloid Neoplasia.Current hematologic malignancy reports · 2020
    Review
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

13 authors.

Lauren L RitterhouseDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA. lritterhouse@partners.org.ORCID http://orcid.org/0000-0002-7655-630X
Megan ParillaDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Chao Jie ZhenDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Michelle N WurstDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Rutika PuranikDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Candace M HendersonDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Neda Z JoudehDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Madeline J HartleyDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Rishikesh HaridasDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Pankhuri WanjariDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Larissa V FurtadoDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Sabah KadriDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.
Jeremy P SegalDivision of Genomic and Molecular Pathology, Department of Pathology, University of Chicago Medicine, Chicago, IL, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNucleophosmin 1 (NPM1) is one of the most commonly mutated genes in acute myeloid leukemia, with mutations observed in approximately 30% of all adult cases. The persistence of NPM1 mutations following chemotherapy is associated with a greater risk of relapse as well as a lower rate of survival, making NPM1 measurable residual disease (MRD) an informative clinical target.

methodsHerein, we have developed a straightforward unique molecular identifier (UMI)-based amplicon next-generation sequencing method for the detection of NPM1-mutated MRD that addresses some of the limitations present in other assays.

resultsThe NPM1 assay allowed for accurate counting of individual mutant and wild-type molecules down to 0.01% variant allelic frequency. In silico contamination experiments highlighted the ability of this UMI methodology to maximize specificity through dramatic reductions in sequencing/demultiplexing bleed-through error.

conclusionPerformance and clinical utility of the NPM1 MRD assay are established via both validation experiments and analyses of live performance over 1.5 years of routine clinical service.

Indexed as

Biomarkers, TumorHigh-Throughput Nucleotide SequencingHumansLeukemia, Myeloid, AcuteLimit of DetectionMutationNeoplasm, ResidualNuclear ProteinsNucleophosminRecurrenceSensitivity and SpecificitySequence Analysis, DNABiomarkers, TumorNPM1 protein, humanNuclear ProteinsNucleophosmin

Identifiers

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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.