Evidence map›Paper›PMID 26384303›Full record

ArticleOncotarget2015

Revealing very small FLT3 ITD mutated clones by ultra-deep sequencing analysis has important clinical implications in AML patients.

Elisa Zuffa, Eugenia Franchini, Cristina Papayannidis, Carmen Baldazzi, Giorgia Simonetti, Nicoletta Testoni, Maria Chiara Abbenante, Stefania Paolini, Chiara Sartor, Sarah Parisi and 7 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. MRD evaluation of AML in clinical practice: are we there yet?Hematology. American Society of Hematology. Education Program · 2019
    Review
  8. Article
  9. Review
  10. Clonal heterogeneity ofOncotarget · 2018
    Article
  11. FLT3-ITD and its current role in acute myeloid leukaemia.Medical oncology (Northwood, London, England) · 2017
    Review
  12. Article
  13. 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

17 authors at 2 institutions in 1 country.

Elisa Zuffa"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Eugenia Franchini"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Cristina Papayannidis"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Carmen Baldazzi"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Giorgia Simonetti"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Nicoletta Testoni"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Maria Chiara Abbenante"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Stefania Paolini"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Chiara Sartor"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Sarah Parisi"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Giovanni Marconi"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Federica CattinaBone Marrow Transplant Unit, University of Brescia, Brescia, Italy.
Maria Teresa Bochicchio"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Claudia Venturi"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Emanuela Ottaviani"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Michele Cavo"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Giovanni Martinelli"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
Policlinico S.Orsola-Malpighi · ITUniversity of Brescia · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

FLT3 internal tandem duplication (ITD), one of the most frequent mutations in Acute Myeloid Leukemia (AML), is reported to be an unstable marker, as it can evolve from FLT3 ITD- to ITD+ during the disease course. A single-gene sensitive mutational screening approach may be helpful for better clarifying the exact timing of mutation occurrence, especially when FLT3 ITD appears to occur late, at disease progression. We developed an amplicon-based ultra-deep-sequencing (UDS) approach for FLT3 mutational screening. We exploited this highly sensitive technology for the retrospective screening of diagnosis, relapse and follow-up samples of 5 out of 256 cytogenetically normal (CN-) AML who were FLT3 wild-type at presentation, but tested ITD+ at relapse or disease progression. Our study revealed that all patients carried a small ITD+ clone at diagnosis, which was undetectable by routine analysis (0,2-2% abundance). The dynamics of ITD+ clones from diagnosis to disease progression, assessed by UDS, reflected clonal evolution under treatment pressure. UDS appears as a valuable tool for FLT3 mutational screening and for the assessment of minimal residual disease (MRD) during follow-up, by detecting small ITD+ clones that may survive chemotherapy, evolve over time and definitely worsen the prognosis of CN-AML patients.

Indexed as

AdultAgedFemalefms-Like Tyrosine Kinase 3Follow-Up StudiesHigh-Throughput Nucleotide SequencingHumansLeukemia, Myeloid, AcuteMaleMiddle AgedMutationNeoplasm, ResidualNeoplasm StagingPrognosisReal-Time Polymerase Chain ReactionRetrospective StudiesFLT3 protein, humanfms-Like Tyrosine Kinase 3RNA, MessengerAMLclonal evolutionFLT3minimal residual diseaseultra-deep sequencing

Identifiers

PMID26384303
PMCPMC4741605
OpenAlexW2255536169

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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.