Polyclonal versus compound mutations. In a subset of patients who develop clinical resistance to ABL1 TKIs, more than 1 point mutation in the kinase domain of BCR-ABL1 is detectable by direct sequencing. In the case of polyclonal mutations, these BCR-ABL1 mutations (green and red stars; top panel) exist separately in different clones. In contrast, BCR-ABL1 compound mutants exhibit 2 mutations within the same BCR-ABL1 molecule (green and red stars; bottom panel).