How will genomic testing impact a clinician's choice for managing chronic myeloid leukemia?

Chronic myeloid leukemia (CML) is a disease characterized by a single diagnostic molecular abnormality and epitomizes a genetically based diagnosis and management. Targeted therapy with tyrosine kinase inhibitors has revolutionized treatment and prognosis of this disease; however, a proportion of patients will experience resistance to therapy and progress to blast phase, the terminal phase of this disease. Emerging genomic profiling in CML reveals a genetically heterogenous landscape which may permit further risk stratification, personalization of treatment, and the potential for drug development.This review encompasses original literature exploring the genomic profile of CML and the potential impact of additional genomic abnormalities on prognosis and treatment response.

Somatic variants in cancer-associated genes, particularly ASXL1, are of prognostic and potential therapeutic significance in CML. Up-front next-generation sequencing is therefore useful when available in all patients with newly diagnosed CML and repeat testing should be considered at timepoints of suboptimal treatment response, TKI resistance, and progression. Gene rearrangements and fusions are an emerging class of mutation that may confer adverse prognostic risk and hence use of a robust testing method that enables detection of such abnormalities is desirable.