Figure 4
Figure 4. Simultaneous evolution of compound mutant clones at comparable levels. Cloning and sequencing of 55 colonies for CML#14 revealed a complex pattern of compound mutations. There were at least 3 major classes of clones (F359V/T315I, K294K/M351T/V299L, and E355G) and their derivatives, which formed the majority of the BCR-ABL1 clones in this sample. The thick red, green, and blue circles represent 11, 6, and 14 clones, respectively. The dotted circle represents a clone that was not detected but was expected to be the parent of the 2 observed clones. The remaining circles represent clones detected a single time. These single clone results should be interpreted with caution because PCR error can never be rigorously excluded. Silent mutations are labeled in red. There is a marked increase in the proportion of silent mutations as clones acquire additional mutations. One clone presumably destined for immediate elimination has a stop mutation (E355G/Q300Stop) expected to abolish kinase activity in the middle of the kinase domain.

Simultaneous evolution of compound mutant clones at comparable levels. Cloning and sequencing of 55 colonies for CML#14 revealed a complex pattern of compound mutations. There were at least 3 major classes of clones (F359V/T315I, K294K/M351T/V299L, and E355G) and their derivatives, which formed the majority of the BCR-ABL1 clones in this sample. The thick red, green, and blue circles represent 11, 6, and 14 clones, respectively. The dotted circle represents a clone that was not detected but was expected to be the parent of the 2 observed clones. The remaining circles represent clones detected a single time. These single clone results should be interpreted with caution because PCR error can never be rigorously excluded. Silent mutations are labeled in red. There is a marked increase in the proportion of silent mutations as clones acquire additional mutations. One clone presumably destined for immediate elimination has a stop mutation (E355G/Q300Stop) expected to abolish kinase activity in the middle of the kinase domain.

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