Table II.

BCR-ABL1 mutations in K562 cells

Construct transduced Treatment BCR-ABL1 sequence analysis Number of clones/total Amino acid change 
GFP Imatinib Unmutated 6/8 No changes 
  894 CTA to CTG 1/8 Silent 
  1062 CTA to CTG 1/8 Silent 
AID-ires-GFP Control Unmutated 7/9 No changes 
  894 CTA to CTG 1/9 Silent 
  1062 CTA to CTG 1/9 Silent 
AID-ires-GFP Imatinib Unmutated 2/10 No changes 
  894 CTA to CTG 3/10 Silent 
  944 ACT to ATT 4/10 T315I 
  1062 CTA to CTG 2/10 Silent 
  1334/1335 CGT to CTG 1/10 R445L 
  1356 CTA to CTG 2/10 Silent 
  1375 GAG to AAG 3/10 E459K 
AID-ires-GFP Imatinib + 17-AAG Unmutated 6/9 No changes 
  894 CTA to CTG 1/9 Silent 
  1062 CTA to CTG 2/9 Silent 
Construct transduced Treatment BCR-ABL1 sequence analysis Number of clones/total Amino acid change 
GFP Imatinib Unmutated 6/8 No changes 
  894 CTA to CTG 1/8 Silent 
  1062 CTA to CTG 1/8 Silent 
AID-ires-GFP Control Unmutated 7/9 No changes 
  894 CTA to CTG 1/9 Silent 
  1062 CTA to CTG 1/9 Silent 
AID-ires-GFP Imatinib Unmutated 2/10 No changes 
  894 CTA to CTG 3/10 Silent 
  944 ACT to ATT 4/10 T315I 
  1062 CTA to CTG 2/10 Silent 
  1334/1335 CGT to CTG 1/10 R445L 
  1356 CTA to CTG 2/10 Silent 
  1375 GAG to AAG 3/10 E459K 
AID-ires-GFP Imatinib + 17-AAG Unmutated 6/9 No changes 
  894 CTA to CTG 1/9 Silent 
  1062 CTA to CTG 2/9 Silent 

Identity of the mutations indicated in the diagram in Fig. 7 E. The BCR-ABL1 (exon 13 of BCR and exon 9 of ABL1) was RT-PCR amplified from single cell clones, and a fragment of ∼700 bp in the ABL1 kinase domain was directly sequenced. The number to the left of the mutation indicates the mutated position with respect to the ABL1 open reading frame. The mutated base is underlined within the affected codon. Mutations at C:G pairs and amino acid substitutions previously described to confer clinical imatinib resistance (Branford and Hughes, 2006) are highlighted in bold.

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