Journal article

Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemia

Deborah White, Verity Saunders, Andrew Grigg, Chris Arthur, Robin Filshie, Michael F Leahy, Kevin Lynch, L Bik To, Timothy Hughes

JOURNAL OF CLINICAL ONCOLOGY | AMER SOC CLINICAL ONCOLOGY | Published : 2007

Abstract

PURPOSE: Intrinsic sensitivity to imatinib, based on measurement of inhibitory concentration 50% for imatinib, is variable in untreated patients with chronic myeloid leukemia (CML). This suggests that patient-tailored dosing may be more rational than a fixed dose for all. Dose optimization potentially could be based on accurate measurement of the level of BCR-ABL kinase inhibition achieved in vivo. PATIENTS AND METHODS: In vivo kinase inhibition was measured by calculating the reduction in protein (p)--Crkl level in mononuclear blood cells taken from 49 CML patients at weekly intervals after imatinib therapy was commenced. RESULTS: Greater than 50% inhibition (> 50% reduction in p-Crkl from ..

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