Quantitative Analysis of Mutant Subclones in Chronic Myeloid Leukemia: Comparison of Different Methodological Approaches

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Identification and quantitative monitoring of mutant BCR-ABL1 subclones displaying resistance to tyrosine kinase inhibitors (TKIs) have become important tasks in patients with Ph-positive leukemias. Different technologies have been established for patient screening. Various next-generation sequencing (NGS) platforms facilitating sensitive detection and quantitative monitoring of mutations in the ABL1-kinase domain (KD) have been introduced recently, and are expected to become the preferred technology in the future. However, broad clinical implementation of NGS methods has been hampered by the limited accessibility at different centers and the current costs of analysis which may not be regarded as readily affordable for routine diagnostic monitoring. It is therefore of interest to determine whether NGS platforms can be adequately substituted by other methodological approaches. We have tested three different techniques including pyrosequencing, LD (ligation-dependent)-PCR and NGS in a series of peripheral blood specimens from chronic myeloid leukemia (CML) patients carrying single or multiple mutations in the BCR-ABL1 KD. The proliferation kinetics of mutant subclones in serial specimens obtained during the course of TKI-treatment revealed similar profiles via all technical approaches, but individual specimens showed statistically significant differences between NGS and the other methods tested. The observations indicate that different approaches to detection and quantification of mutant subclones may be applicable for the monitoring of clonal kinetics, but careful calibration of each method is required for accurate size assessment of mutant subclones at individual time points.

Detaljer

Författare
  • Sandra Preuner
  • Agnes Barna
  • Florian Frommlet
  • Stefan Czurda
  • Byrgazov Konstantin
  • Mary Alikian
  • Katerina Machova Polakova
  • Tomasz Sacha
  • Johan Richter
  • Thomas Lion
  • Christian Gabriel
Enheter & grupper
Externa organisationer
  • Medical University of Vienna
  • Skåne University Hospital
  • St. Anna Children's Hospital
  • Red Cross Blood Transfusion Service of Upper Austria
  • Imperial College London
  • Hammersmith Hospital
  • Institute of Hematology and Blood Transfusion
  • Jagellonian University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
  • Cell- och molekylärbiologi

Nyckelord

Originalspråkengelska
TidskriftInternational Journal of Molecular Sciences
Volym17
Utgivningsnummer5
StatusPublished - 2016 apr 29
PublikationskategoriForskning
Peer review utfördJa