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ShRNA library screening identifies nucleocytoplasmic transport as a mediator of BCR-ABL1 kinase-independent resistance by Jamshid S. Khorashad, Anna M.

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Presentation on theme: "ShRNA library screening identifies nucleocytoplasmic transport as a mediator of BCR-ABL1 kinase-independent resistance by Jamshid S. Khorashad, Anna M."— Presentation transcript:

1 shRNA library screening identifies nucleocytoplasmic transport as a mediator of BCR-ABL1 kinase-independent resistance by Jamshid S. Khorashad, Anna M. Eiring, Clinton C. Mason, Kevin C. Gantz, Amber D. Bowler, Hannah M. Redwine, Fan Yu, Ira L. Kraft, Anthony D. Pomicter, Kimberly R. Reynolds, Anthony J. Iovino, Matthew S. Zabriskie, William L. Heaton, Srinivas K. Tantravahi, Michael Kauffman, Sharon Shacham, Alex Chenchik, Kyle Bonneau, Katharine S. Ullman, Thomas O’Hare, and Michael W. Deininger Blood Volume 125(11):1772-1781 March 12, 2015 ©2015 by American Society of Hematology

2 K562R and AR230R cells are resistant to imatinib despite inhibition of BCR-ABL1 kinase. Jamshid S. Khorashad et al. Blood 2015;125:1772-1781 ©2015 by American Society of Hematology

3 Experimental design and reproducibility. Jamshid S. Khorashad et al. Blood 2015;125:1772-1781 ©2015 by American Society of Hematology

4 Validation of selected candidates from the lentiviral screen. Jamshid S. Khorashad et al. Blood 2015;125:1772-1781 ©2015 by American Society of Hematology

5 Cytoplasmic RAN contributes to BCR-ABL1 kinase-independent TKI resistance. Jamshid S. Khorashad et al. Blood 2015;125:1772-1781 ©2015 by American Society of Hematology

6 Ectopic expression of RanGAP confers resistance to imatinib. Jamshid S. Khorashad et al. Blood 2015;125:1772-1781 ©2015 by American Society of Hematology

7 Enhanced RAN/XPO1 shuttling activity is associated with enhanced levels of cytoplasmic SET in TKI-resistant CML cell lines. Jamshid S. Khorashad et al. Blood 2015;125:1772-1781 ©2015 by American Society of Hematology

8 Inhibition of RAN/XPO1 impairs survival of CML but not normal CD34+ cord blood cells. Jamshid S. Khorashad et al. Blood 2015;125:1772-1781 ©2015 by American Society of Hematology


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