title: Molecular monitoring of chronic myeloid leukemia: present and future.
abstract: 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.
authors.affiliation: a Clinical Research Division , Fred Hutchinson Cancer Research Center Ringgold standard institution , Seattle , WA , USA.|b Pathology , University of Washington School of Medicine Ringgold standard institution , Seattle , WA , USA.
authors.forename: Cecilia Ching Sze
authors.initials: CC
authors.lastname: Yeung
authors.affiliation: a Clinical Research Division , Fred Hutchinson Cancer Research Center Ringgold standard institution , Seattle , WA , USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Egan
authors.affiliation: c Fred Hutchinson Cancer Research Center , Seattle , WA , USA.
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
mesh_terms: D014408:Biomarkers, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D019095:Point-of-Care Systems; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1 transcript levels; Chronic myeloid leukemia; molecular diagnostics; monitoring; tyrosine kinase inhibitor resistance mutations