Impact of BCR::ABL1 transcript type on RT-qPCR amplification performance and molecular response to therapy

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Matthew Salmon - , University of Southampton (Autor:in)
  • Helen E White - , University of Southampton (Autor:in)
  • Hana Zizkova - , Institute of Hematology and Blood Transfusion (Autor:in)
  • Andrea Gottschalk - , Institut für Medizinische Informatik und Biometrie (Autor:in)
  • Eliska Motlova - , Institute of Hematology and Blood Transfusion (Autor:in)
  • Nuno Cerveira - , Instituto Português de Oncologia (IPO) do Porto (Autor:in)
  • Dolors Colomer - , August Pi i Sunyer Biomedical Research Institute (Autor:in)
  • Daniel Coriu - , Fundeni Clinical Institute (Autor:in)
  • Georg N Franke - , Universität Leipzig (Autor:in)
  • Enrico Gottardi - , University of Turin (Autor:in)
  • Barbara Izzo - , University of Naples Federico II (Autor:in)
  • Tomas Jurcek - , Masaryk University (Autor:in)
  • Thomas Lion - , Labdia Labordiagnostik / St. Anna Children´s Cancer Research Institute (CCRI) (Autor:in)
  • Vivien Schäfer - , Universitätsklinikum Jena (Autor:in)
  • Claudia Venturi - , IRCSS Azienda Ospedaliero-Universitaria di Bologna (Autor:in)
  • Paolo Vigneri - , University of Catania (Autor:in)
  • Magdalena Zawada - , The University Hospital in Krakow (Autor:in)
  • Jan Zuna - , Universitätskrankenhaus Motol (Autor:in)
  • Lenka Hovorkova - , Universitätskrankenhaus Motol (Autor:in)
  • Jitka Koblihova - , Institute of Hematology and Blood Transfusion (Autor:in)
  • Hana Klamova - , Institute of Hematology and Blood Transfusion (Autor:in)
  • Marketa Stastna Markova - , Institute of Hematology and Blood Transfusion (Autor:in)
  • Dana Srbova - , Institute of Hematology and Blood Transfusion (Autor:in)
  • Adela Benesova - , Institute of Hematology and Blood Transfusion (Autor:in)
  • Vaclava Polivkova - , Institute of Hematology and Blood Transfusion (Autor:in)
  • Daniela Zackova - , Masaryk University (Autor:in)
  • Jiri Mayer - , Masaryk University (Autor:in)
  • Ingo Roeder - , Institut für Medizinische Informatik und Biometrie, Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg, Deutsches Krebsforschungszentrum (DKFZ), Universität Heidelberg, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Ingmar Glauche - , Institut für Medizinische Informatik und Biometrie (Autor:in)
  • Thomas Ernst - , Universitätsklinikum Jena (Autor:in)
  • Andreas Hochhaus - , Universitätsklinikum Jena (Autor:in)
  • Katerina Machova Polakova - , Institute of Hematology and Blood Transfusion (Autor:in)
  • Nicholas C P Cross - , University of Southampton (Autor:in)

Abstract

Several studies have reported that chronic myeloid leukaemia (CML) patients expressing e14a2 BCR::ABL1 have a faster molecular response to therapy compared to patients expressing e13a2. To explore the reason for this difference we undertook a detailed technical comparison of the commonly used Europe Against Cancer (EAC) BCR::ABL1 reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assay in European Treatment and Outcome Study (EUTOS) reference laboratories (n = 10). We found the amplification ratio of the e13a2 amplicon was 38% greater than e14a2 (p = 0.015), and the amplification efficiency was 2% greater (P = 0.17). This subtle difference led to measurable transcript-type dependent variation in estimates of residual disease which could be corrected by (i) taking the qPCR amplification efficiency into account, (ii) using alternative RT-qPCR approaches or (iii) droplet digital PCR (ddPCR), a technique which is relatively insensitive to differences in amplification kinetics. In CML patients, higher levels of BCR::ABL1/GUSB were identified at diagnosis for patients expressing e13a2 (n = 67) compared to e14a2 (n = 78) when analysed by RT-qPCR (P = 0.0005) but not ddPCR (P = 0.5). These data indicate that widely used RT-qPCR assays result in subtly different estimates of disease depending on BCR::ABL1 transcript type; these differences are small but may need to be considered for optimal patient management.

Details

OriginalspracheEnglisch
Seiten (von - bis)1879-1886
Seitenumfang8
FachzeitschriftLeukemia
Jahrgang36
Ausgabenummer7
PublikationsstatusVeröffentlicht - Juli 2022
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC9252903
Scopus 85131514188
unpaywall 10.1038/s41375-022-01612-2
ORCID /0000-0002-2524-1199/work/142251494

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Fusion Proteins, bcr-abl/genetics, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis, Neoplasm, Residual/genetics, Real-Time Polymerase Chain Reaction