Evidence map›Paper›PMID 26446915›Full record

ArticleMolecular diagnosis & therapy2015

A Novel Tandem Duplication Assay to Detect Minimal Residual Disease in FLT3/ITD AML.

Ming-Tseh Lin, Li-Hui Tseng, Jonathan C Dudley, Stacey Riel, Harrison Tsai, Gang Zheng, Keith W Pratz, Mark J Levis, Christopher D Gocke

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular diagnosis & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–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

4 citing papers in PubMed.

  1. Review
  2. MRD evaluation of AML in clinical practice: are we there yet?Hematology. American Society of Hematology. Education Program · 2019
    Review
  3. Review
  4. 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

9 authors.

Ming-Tseh LinDivision of Molecular Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Park SB202, 600 North Wolfe Street, Baltimore, MD, 21287, USA.
Li-Hui TsengDivision of Molecular Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Park SB202, 600 North Wolfe Street, Baltimore, MD, 21287, USA.
Jonathan C DudleyDivision of Molecular Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Park SB202, 600 North Wolfe Street, Baltimore, MD, 21287, USA.
Stacey RielDivision of Molecular Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Park SB202, 600 North Wolfe Street, Baltimore, MD, 21287, USA.
Harrison TsaiDivision of Molecular Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Park SB202, 600 North Wolfe Street, Baltimore, MD, 21287, USA.
Gang ZhengDivision of Molecular Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Park SB202, 600 North Wolfe Street, Baltimore, MD, 21287, USA.
Keith W PratzDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mark J LevisDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christopher D GockeDivision of Molecular Pathology, Department of Pathology, Johns Hopkins University School of Medicine, Park SB202, 600 North Wolfe Street, Baltimore, MD, 21287, USA. cgocke1@jhmi.edu.ORCID http://orcid.org/0000-0002-9541-2192

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
The Johns Hopkins Translational Science Team for the ET-CTNUM1CA186691 · NCI · JOHNS HOPKINS UNIVERSITY · PI Jan Hendrik Beumer, Michael A Carducci · 2014 to 2026
$21.9M
A Method for Rapid Long-range Direct HaplotypingR21HG004315 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI GOCKE, CHRISTOPHER D · 2007 to 2008
$451k
Assaying the Combinatorial TranscriptomeR21HG005745 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI GOCKE, CHRISTOPHER D · 2010 to 2011
$447k
NCI NIH HHS 1UM1CA186691-01NCI NIH HHS P30 CA006973NCI NIH HHS UM1 CA186691NHGRI NIH HHS R21 HG004315NHGRI NIH HHS R21HG004315NHGRI NIH HHS R21 HG005745NHGRI NIH HHS R21HG005745
6 · The paper itself

Abstract

backgroundInternal tandem duplication (ITD) of the fms-related tyrosine kinase 3 (FLT3) gene is associated with a poor prognosis in acute myeloid leukemia (AML) patients with a normal karyotype. The current standard polymerase chain reaction (PCR) assay for FLT3/ITD detection is not sufficiently sensitive to monitor minimal residual disease (MRD). Clone-specific assays may have sufficient sensitivity but are not practical to implement, since each clone-specific primer/probe requires clinical validation.

objectiveTo develop an assay for clinical molecular diagnostics laboratories to monitor MRD in FLT3/ITD AMLs.

methodsWe designed a simple novel assay, tandem duplication PCR (TD-PCR), and tested its sensitivity, specificity, and clinical utility in FLT3/ITD AML patients.

resultsTD-PCR was capable of detecting a single ITD molecule and was applicable to 75 % of ITD mutants tested. TD-PCR detected MRD in bone marrow prior to patient relapse. TD-PCR also identified low-level ITD mutants not only in FLT3/ITD AMLs but also in initial diagnostic specimens that were reportedly negative by the standard assay in patients who progressed with the same ITDs detected by the TD-PCR assay.

conclusionDetection of MRD by TD-PCR may guide patient selection for early clinical intervention. In contrast to clone-specific approaches, the TD-PCR assay can be more easily validated for MRD detection in clinical laboratories because it uses standardized primers and a universal positive control. In addition, our findings on multi-clonality and low-level ITDs suggest that further studies are warranted to elucidate their clinical/biological significance.

Indexed as

DNA Mutational Analysisfms-Like Tyrosine Kinase 3Gene DuplicationHumansLeukemia, Myeloid, AcuteMolecular Diagnostic TechniquesNeoplasm, ResidualPolymerase Chain ReactionSensitivity and SpecificityFLT3 protein, humanfms-Like Tyrosine Kinase 3

Identifiers

PMID26446915
PMCPMC4655128

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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.