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Synergistic effect of imatinib mesylate and fludarabine combination on Philadelphia chromosome-positive chronic myeloid leukemia cell lines
Fludarabine-containing combinations have additive cell killing against leukemic blasts in vitro. It has also been shown that imatinib mesylate combined with fludarabine or cladribine had an additive effect on CML CFU-GM cells. In this regard, we aimed to investigate the effect of fludarabine-imatinib mesylate combination against CML blastic phase cell lines K562 and Meg-01. XTT test was performed for proliferation and inhibition assay. According to obtained data, five different effective concentrations of each drug in 25 different combinations were tested. Results of the combination studies were analyzed with isobologram. At IC20, imatinib mesylate and fludarabine combination showed synergism and strong synergism in K562 and Meg-01 cells, respectively. At IC50 and IC75, combination indexes (CI) indicated strong synergism and synergism. Based on our results, the fludarabine- based chemotherapy regimens can be used for those patients with CML blastic phase in combination with imatinib mesylate.

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Authors: Özden Pişkin, Mehmet Ali Özcan, Güner Hayri Özcan, Halil Ateş, Fatih Demirkan, İnci Alacacıoğlu, Bülent Ündar

Keywords: Fludarabin, imatinib mesilat, KML, K562, Meg-01

  • Year: 2007
  • Number: 1
  • Referance No: 00710

  • Figure 1. Dose-effect curves of cell lines; A: STI571 for K562, B: Fludarabine for K562 and C: STI571 for Meg-01, D: Fludarabine for Meg-01.
  • Figure 2. Isobologram analyses of K562 (A) and Meg-01 (B).

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