It remains unclear whether BTK or PLCG2 mutations are fully responsible for the survival of the whole CLL cell clone on therapy/during relapse since they are often present in a small CLL cell subpopulation (<5% variant allele frequency [VAF]) (8, 9), and 20%–35% of relapsing CLL patients do not carry mutations explaining the resistance (57–59). The gene discussed is BTK; the disease is B-cell chronic lymphocytic leukemia.