Analytical Validation of a Highly Sensitive, Multiplexed Chronic Myeloid Leukemia Monitoring System Targeting BCR-ABL1 RNA

Justin T. Brown, Ion J. Beldorth, Walairat Laosinchai-Wolf, Marie E. Fahey, Keri L. Jefferson, Adam K. Ruskin, Jacquelyn J. Roth, Li Cai, Christopher D. Watt, Richard D. Press, Fei Yang, John B. Hedges, Bernard F. Andruss

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

This study describes the analytical performance of the QuantideX qPCR BCR-ABL IS Kit, the first Food and Drug Administration–cleared assay designed to monitor breakpoint cluster region–Abelson tyrosine-protein kinase 1 (BCR-ABL1) fusion transcripts isolated from peripheral blood specimens from patients with chronic myeloid leukemia. This multiplex real-time quantitative RT-PCR assay amplifies both e13a2 and e14a2 Major BCR-ABL1 transcripts and the reference target ABL1. The test results are provided in international scale (IS) values by incorporating armored RNA-based calibrators that have defined IS values tied directly to the World Health Organization BCR-ABL1 Primary Reference Materials, without the necessity of determining and maintaining conversion factors. For each batch run, the integrated interpretive software evaluates run and specimen quality control metrics (including a sufficient amount of ABL1 control transcripts to ensure a minimal limit of detection) and calculates both molecular response (MR) and %IS values for each specimen. The test has a limit of detection of MR4.7 (0.002%IS) and a linear range from MR0.3 (50%IS) to MR4.7 (0.002%IS) for both Major transcripts. Single-site and multisite precision studies demonstrated a maximum SD of 0.13 MR (30% CV within the assay range between MR0.7 and MR3.7). The performance of this BCR-ABL1 monitoring test meets all of the clinical guideline recommendations for sensitivity and IS reporting for the management of chronic myeloid leukemia patients.

Original languageEnglish (US)
Pages (from-to)718-733
Number of pages16
JournalJournal of Molecular Diagnostics
Volume21
Issue number4
DOIs
StatePublished - Jul 2019

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

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