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  • Title: Phosphorylation levels of BCR-ABL, CrkL, AKT and STAT5 in imatinib-resistant chronic myeloid leukemia cells implicate alternative pathway usage as a survival strategy.
    Author: Jilani I, Kantarjian H, Gorre M, Cortes J, Ottmann O, Bhalla K, Giles FJ, Albitar M.
    Journal: Leuk Res; 2008 Apr; 32(4):643-9. PubMed ID: 17900686.
    Abstract:
    Ex-vivo studies have suggested that imatinib-resistance in chronic myeloid leukemia (CML) patients occurs despite adequate suppression of BCR-ABL activity. Whether BCR-ABL phosphorylation levels differ between imatinib-sensitive and -resistant patients is not known. We compared the phosphorylation of BCR-ABL in 54 previously untreated CML patients and 62 imatinib-resistant CML patients with progressive disease. Resistant patients had significantly lower levels of BCR-ABL, CrkL and AKT phosphorylation than previously untreated patients, but STAT5 phosphorylation showed no difference. These observations suggest that imatinib- resistance is not necessarily dependent on higher activity in BCR-ABL-dependent pathways, but is likely due to the activation of other pathways.
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