Sequence analysis of 2 patients with point mutations in the ATP binding site.

The 863-bp RT-PCR products of the ABL kinase domain of BCR/ABL were sequenced. Arrows indicate the mutated nucleotide. (A) A point mutation was first detected in patient 20 (Table 1) at the eighth month of imatinib therapy. A mix of mutant and wild-type BCR/ABL was evident from months 8 to 11. The predominant nucleotide switched from wild-type to mutant over the course of 4 months. Sequence Navigator software (Applied Biosystems, Foster City, CA) was unable to distinguish between the wild-type and mutant nucleotides at months 9 and 10, as indicated by N at the mutated site. The patient remains in accelerated phase. (B) Patient 1 (Table 1) had a complete cytogenetic response (CCR) to imatinib therapy but relapsed into blast crisis at 9 months. The T315I mutation was predominant at that time but was not evident when tested before study in chronic phase or in a previous lymphoid blast crisis sample. The patient was refractory to treatment and has since died.