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Treatment of P190 Bcr/Abl lymphoblastic leukemia cells with inhibitors of the serine/threonine kinase CK2

Leukemia volume 21, pages 178–180 (2007)Cite this article

Chronic myelogenous leukemia (CML) and Ph-positive acute lymphoblastic leukemia (ALL) are caused by the fusion of the BCR gene to the ABL gene, which encodes a tyrosine kinase. The P190 and P210 are two main chimeric forms of the Bcr/Abl protein, with the P190 frequently associated with cases of ALL and P210 predominantly occurring in CML.1 Development of inhibitors such as Imatinib, which specifically target the deregulated Bcr/Abl tyrosine kinase, has revolutionized the treatment of CML.2 However, Philadelphia-positive ALL has a much less durable response to Imatinib and treatment options remain limited.3 Therefore, the identification of signal transduction pathways that are perturbed by Bcr/Abl has become an important area of investigation, aiming to find additional molecular targets for treating this type of cancer.4

We further examined the combined treatment with DMAT and Imatinib. We first treated the cells with 10 μ M DMAT and varied the treatment with Imatinib from 0 to 2.5 μ M. The viability of the cells dropped to 30% after 24 h of treatment with DMAT alone, and was further reduced after 2 days of treatment. Consistent with the results in Figures 2a and 3a however, some viable cells persisted in the culture. The addition of Imatinib clearly resulted in a further decrease in viable cell numbers, and with the addition of 1.25 μ M drug, all cells were killed within 34 h (Figure 3c). As the combination of 10 μ M Imatinib with 10 μ M DMAT rapidly killed the cells (Figure 3a), we also treated the cells with a lower fixed concentration of 5 μ M Imatinib and added 0–5 μ M DMAT to the cultures. Treatment with 5 μ M Imatinib alone for 24 h caused a decrease to 55% in cell viability and the addition of DMAT further enhanced this effect (Figure 3d).

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Acknowledgements

We thank Jess Cunnick for advice and help with the leukemia–MEF co-culture system. This work was supported by PHS Grant CA90321 (NH), the Kenneth T and Eileen L Norris Foundation (SM, VP, BZ, PK, JG) and the TJ Martell Foundation (JG and NH) and by AIRC and Integrated EU Project ‘Orokinase Research’ LSHB-CT-2004-503467 (LAP).

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  1. S Mishra

    Present address: Department of Pediatrics, Division of Research Immunology and Bone Marrow Transplantation, Childrens Hospital Los Angeles, LA, USA

Authors and Affiliations

  1. Department of Pediatrics, Division of Hematology/Oncology, Childrens Hospital Los Angeles Saban Research Institute and the Keck School of Medicine, University of Southern California, LA, USA

    S Mishra, V Pertz, B Zhang, P Kaur, J Groffen & N Heisterkamp

  2. Department of Pathology, Childrens Hospital Los Angeles Saban Research Institute and the Keck School of Medicine, University of Southern California, LA, USA

    H Shimada

  3. Department of Experimental Pharmacology, Laboratory of Experimental Pharmacology, Polish Academy of Sciences Medical Research Center, Warsaw, Poland

    Z Kazimierczuk

  4. Department of Biological Chemistry, University of Padova and Venetian Institute for Molecular Medicine, Padova, Italy

    L A Pinna

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Mishra, S., Pertz, V., Zhang, B. et al. Treatment of P190 Bcr/Abl lymphoblastic leukemia cells with inhibitors of the serine/threonine kinase CK2. Leukemia 21, 178–180 (2007). https://doi.org/10.1038/sj.leu.2404460

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