Open Access Research article

Overcoming Bcr-Abl T315I mutation by combination of GNF-2 and ATP competitors in an Abl-independent mechanism

Mamduh Khateb1, Nili Ruimi1, Hazem Khamisie1, Yousef Najajreh2, Afsar Mian3, Anna Metodieva3, Martin Ruthardt3 and Jamal Mahajna14*

Author Affiliations

1 Cancer Drug Discovery Program, Galilee Technology Center, Migal, P.O.Box 831, Kiryat Shmona, 11016, Israel

2 Faculty of Pharmacy, Al-Quds University, Jerusalem-Abu Dies, Palestine

3 Medizinische Klinik II/Abt. Hämatologie, Klinikum der Goethe-Universität, Theodor-Stern Kai 7, 60590, Frankfurt, Germany

4 Department of Nutritional Sciences, Tel-Hai College, Kiryat Shmona, Israel

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BMC Cancer 2012, 12:563  doi:10.1186/1471-2407-12-563

Published: 27 November 2012

Additional files

Additional file 1:

Effect of GNF-2 and Abl kinase Inhibitors (AKIs) on the proliferation and clonigenicity of Ba/F3 cells.Figure S1: Effect of Imatinib and Dasatinib on the proliferation of Ba/F3 (Blue) and Ba/F3 p185 Bcr-Abl (Red) cells. The cells supplemented with 10 ng/ml of IL-3, were grown for 72 h in the presence of different Imatinib and Dasatinib concentrations. Cells were counted and percent of inhibition was calculated in relation to the solvent (0.5% DMSO) treated samples. Experiments were carried out in duplicates and repeated twice with comparable outcome. Figure S2: Cooperation between GNF-2 with Imatinib and Dasatinib in regulating proliferation of Ba/F3 cells. Ba/F3 supplemented with 10 ng/ml of IL-3 were grown for 72 h in the presence of various GNF-2 concentration (0.1, 0.5, 2.5, 5, 25 and 125 μM) alone or in combination with Imatinib (1 μM) and Dasatinib (50 nM). After 72 h incubation, cells were counted and percent of inhibition was calculated in relation to the solvent (0.5% DMSO) treated samples. Experiments were carried out in duplicates and repeated twice with comparable outcome. Figure S3: Effect of GNF-2 and AKIs on the clonigenicity of Ba/F3 cells. Ba/F3 cells grown on soft agar were treated with solvent (DMSO 0.5%; Un), Imatinib (1 μM), Dasatinib (1 μM), and GNF-2 (5 μM-100 μM) alone or in the presence of either 1 μM Imatinib or 1 μM Dasatinib. Experiments were carried out in duplicates and repeated twice with comparable outcome.

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