Evidence map›Paper›PMID 35908105›Full record

ArticleLeukemia2022

Droplet digital PCR for the detection of second-generation tyrosine kinase inhibitor-resistant BCR::ABL1 kinase domain mutations in chronic myeloid leukemia.

Simona Soverini, Sara De Santis, Margherita Martelli, Cecilia Monaldi, Fausto Castagnetti, Gabriele Gugliotta, Cristina Papayannidis, Manuela Mancini, Samantha Bruno, Claudia Venturi and 5 more

Abstract read
PubMed Publisher
In one paragraph

Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 3% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Guideline
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  3. Review
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  5. Article
  6. Article
  7. Article
  8. Resistance mutations in CML and how we approach them.Hematology. American Society of Hematology. Education Program · 2023
    Review
  9. Review
  10. Article
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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

15 authors at 6 institutions in 5 countries.

Simona SoveriniDipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università di Bologna, Bologna, Italy. simona.soverini@unibo.it.ORCID http://orcid.org/0000-0002-4508-0353
Sara De Santis *Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università di Bologna, Bologna, Italy.
Margherita Martelli *Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università di Bologna, Bologna, Italy.
Cecilia Monaldi *Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università di Bologna, Bologna, Italy.
Fausto CastagnettiIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.
Gabriele GugliottaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.
Cristina PapayannidisIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.
Manuela ManciniIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.
Samantha BrunoDipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università di Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0001-6375-0595
Claudia VenturiIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.
Katerina Machova PolakovaInstitute of Hematology and Blood Transfusion, Prague, Czechia.ORCID http://orcid.org/0000-0002-7398-5555
Thomas ErnstAbteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.ORCID http://orcid.org/0000-0003-2147-489X
Dianna MaarBio-Rad Laboratories, Digital Biology Group, Pleasanton, CA, USA.
Adam CornerBio-Rad Laboratories, Digital Biology Group, Peterborough, UK.
Michele CavoIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0003-4514-3227
Istituto di Ematologia di Bologna · ITUniversity of Bologna · ITBio-Rad (United Kingdom) · GBBio-Rad (United States) · USInstitute of Haematology and Blood Transfusion · CZKlinikum Magdeburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

One of the indications for BCR::ABL1 mutation testing in chronic myeloid leukemia (CML) is when tyrosine kinase inhibitor therapy (TKI) needs to be changed for unsatisfactory response. In this study, we evaluated a droplet digital PCR (ddPCR)-based multiplex strategy for the detection and quantitation of transcripts harbouring mutations conferring resistance to second-generation TKIs (2GTKIs). Parallel quantitation of e13a2, e14a2 and e1a2 BCR::ABL1 fusion transcripts enables to express results as percentage of mutation positive- over total BCR::ABL1 transcripts. We determined the limit of blank in 60 mutation-negative samples. Accuracy was demonstrated by further analysis of 48 samples already studied by next generation sequencing (NGS). Mutations could be called down to 0.5% and across 3-logs of BCR::ABL1 levels. Retrospective review of BCR::ABL1 NGS results in 513 consecutive CML patients with non-optimal response to first- or second-line TKI therapy suggested that a ddPCR-based approach targeted against 2GTKI-resistant mutations would score samples as mutation-negative in 22% of patients with warning response to imatinib but only in 6% of patients with warning response to 2GTKIs. We conclude ddPCR represents an attractive method for easy, accurate and rapid screening for 2GTKI-resistant mutations impacting on TKI selection, although ddPCR cannot identify compound mutations.

Indexed as

Fusion Proteins, bcr-ablLeukemia, Myelogenous, Chronic, BCR-ABL PositiveDrug Resistance, NeoplasmHumansMutationPolymerase Chain ReactionProtein Kinase InhibitorsFusion Proteins, bcr-ablProtein Kinase Inhibitors

Identifiers

PMID35908105
OpenAlexW4288758304

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.