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Not all imatinib resistance in CML are BCR-ABL kinase domain mutations

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Abstract

Point mutations within the ABL kinase domain of the BCR-ABL gene are associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML). To obtain more information about the association between BCR-ABL mutations and type of imatinib resistance, we studied 30 early chronic phase (CP) CML patients, commencing imatinib therapy, using a conventional sequencing technique. Seven patients treated in late CP and three patients treated in the accelerated phase were included for comparison. Blood samples were collected before and every third month during imatinib therapy. Mutations were not seen in any blood sample collected before start of therapy. During imatinib treatment, 2 of the 30 early CP patients acquired point mutations and both of them had other signs of imatinib resistance. None of the five early CP patients with a complete hematologic response (HR), but no cytogenetic response at 12 months, displayed any missense mutation. Likewise, none of 12 early CP patients with detectable BCR-ABL transcripts but in complete hematologic and cytogenetic remission at 12 months displayed any mutation. We conclude that screening early CP patients for BCR-ABL mutations before start of imatinib therapy is not cost-effective. BCR-ABL kinase domain mutations do not appear to explain cytogenetic or molecular (detectable BCR-ABL transcripts by polymerase chain reaction) disease persistence in patients otherwise in stable disease. However, in patients with signs of expanding disease burden, a search for BCR-ABL mutations is warranted.

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Acknowledgements

This study was supported by grants from the Swedish Research Council (project K2002-71X-11630-07B), FoU Västra Götaland, the Swedish Society for Medical Research, “JK Foundation” Sahlgrenska University Hospital, and “Volvo Assar Gabrielssons Foundation.”

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Authors and Affiliations

  1. Department of Internal Medicine/Haematology, Sahlgrenska University Hospital, Gothenburg, 413 45, Sweden

    Yuan Wei, Mats Hardling, Bob Olsson, Rahil Hezaveh, Dick Stockelberg & Hans Wadenvik

  2. Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

    Yuan Wei & Anne Ricksten

  3. Department of Internal Medicine, Shandong University, Qilu Hospital, Jinan, People’s Republic of China

    Yuan Wei

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  1. Yuan Wei
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  2. Mats Hardling
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Correspondence to Hans Wadenvik.

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Wei, Y., Hardling, M., Olsson, B. et al. Not all imatinib resistance in CML are BCR-ABL kinase domain mutations. Ann Hematol 85, 841–847 (2006). https://doi.org/10.1007/s00277-006-0171-8

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  • DOI: https://doi.org/10.1007/s00277-006-0171-8

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