Molecular monitoring of chronic myeloid leukemia: present and future

ABSTRACT

Introduction: Fusion of BCR-ABL1 genes causes chronic myeloid leukemia (CML). As a reliable marker of disease burden, it also serves as the target of tyrosine kinase inhibitors (TKIs). New more sensitive molecular diagnostic tools for BCR-ABL1 can contribute to therapeutic decision-making, especially in considering drug discontinuation for patients enjoying prolonged deep molecular response.

Areas covered: Several novel platforms are transforming CML molecular diagnostics to enable faster point-of-care devices, better understanding of clonal diversity and resistance mutations. Here, we review these molecular platforms, knowing implementation in other hematological malignancies will ensue.

Expert commentary: Treatment with TKI in CML is the first example of a highly effective targeted therapy. Monitoring of BCR-ABL1 mRNA is standard in assessing disease burden being highly predictive of outcomes recommended by both European LeukemiaNet (ELN) and National Comprehensive Cancer Network (NCCN); however, studies has demonstrated poor adherence to these recommendations. In both clinical practice and assay performance, further optimizing of BCR-ABL1 monitoring can be envisioned including point-of-care methods for increased availability of rapid, standardized testing and increasingly sensitive molecular assays that allow for quantification of MRD and detecting resistance mutations.

KEYWORDS:

• Chronic myeloid leukemia
• monitoring
• BCR-ABL1 transcript levels
• molecular diagnostics
• tyrosine kinase inhibitor resistance mutations

Acknowledgments

Bret A Helton, Research technician, Radich Laboratory, Fred Hutchinson Cancer Research Center. Acknowledgment for his image used in Figure 1.

Declaration of interest

CCS Yeung has received research funding from Gilead for unrelated research work. J Radich discloses consulting for Novartis, BMS Ariad and received research funding from Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was partially funded by the NIH/NCI (P01 CA 18029-40) Adult Leukemia Center award (P.I., Appelbaum, F.)- Sub-Project: Molecular Diagnostics.