articleBloodMar 11, 2003BRONZE OA

Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis

SBSusan BranfordZRZbigniew RudzkiSWSonya WalshIPIan ParkinsonAGAndrew Grigg

South Australia Pathology · Novartis (Switzerland) · +5 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Imatinib-treated chronic myeloid leukemia (CML) patients with acquired resistance commonly have detectable BCR-ABL kinase domain mutations. It is unclear whether patients who remain sensitive to imatinib also have a significant incidence of mutations. We evaluated 144 patients treated with imatinib for BCR-ABL kinase domain mutations by direct sequencing of 40 accelerated phase (AP), 64 late chronic phase (> or = 12 months from diagnosis, late-CP), and 40 early-CP patients. Mutations were detected in 27 patients at 17 different residues, 13 (33%) of 40 in AP, 14 (22%) of 64 in late-CP, and 0 of 40 in early-CP. Acquired resistance was evident in 24 (89%) of 27 patients with mutations. Twelve (92%) of 13…

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Topics & keywords

Topics
Keywords
  • Imatinib
  • Mutation
  • Imatinib mesylate
  • Myeloid leukemia
  • Medicine
  • ABL
  • Protein kinase domain
  • Incidence (geometry)
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