Genetic Testings for The Management of CML

Abstract

Molecular analysis of the BCR::ABL1 fusion transcripts is clinically important for the management of CML patients undergoing TKI treatment. This review provides information about the fundamental and current molecular assays essential for managing CML. Chromosome analysis by standard karyotyping is recognized as a standard method for detecting Philadelphia chromosomes and identifying additional chromosomes to assess the patient's risk prior to therapy. FISH has been used for the analysis of the transcriptional variants of BCR::ABL1. Since the level of BCR::ABL1 transcript is reflected in the degree of response to TKIs, quantitative PCR, including traditional qRT-PCR and FDA-approved ddPCR, have been extensively used for specific and sensitive to detect BCR::ABL1 transcript during TKI treatment milestones. Sequencing technologies, including standard direct sequencing and recently high throughput NGS, have been used to identify BCR::ABL1 TKD mutations that contributed to establishing TKI resistance in patients. NGS has several benefits superior to direct sequencing, including detecting low levels of BCR::ABL1 mutations,  discrimination of compound/polyclonal mutations, and identifying more driving mutations besides BCR::ABL1 TKD mutations associated with the establishment of TKI resistance.