Research Papers:

Pre-clinical evidence of PIM kinase inhibitor activity in BCR-ABL1 unmutated and mutated Philadelphia chromosome-positive (Ph+) leukemias

Dany A Curi _, Elspeth M Beauchamp, Gavin T Blyth, Ahmet Dirim Arslan, Nicholas J Donato, Francis J Giles, Jessica K Altman and Leonidas C Platanias

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Oncotarget. 2015; 6:33206-33216. https://doi.org/10.18632/oncotarget.5091

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Dany A. Curi1,2, Elspeth M. Beauchamp1,3,4, Gavin T. Blyth1,3, Ahmet Dirim Arslan1,3, Nicholas J. Donato5, Francis J. Giles1,3, Jessica K. Altman1,3,4, Leonidas C. Platanias1,3,4

1Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA

2Division of Hematology-Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, IL, USA

3Division of Hematology-Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

4Division of Hematology-Oncology, Department of Medicine, Jesse Brown VA Medical Center, Chicago, IL, USA

5Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, MI, USA

Correspondence to:

Leonidas C. Platanias, e-mail: [email protected]

Keywords: CML, PIM kinase, mTOR signaling, philadelphia chromosome-positive leukemia

Received: June 13, 2015     Accepted: August 26, 2015     Published: September 07, 2015


We investigated the efficacy of targeting the PIM kinase pathway in Philadelphia chromosome-positive (Ph+) leukemias. We provide evidence that inhibition of PIM, with the pan-PIM inhibitor SGI-1776, results in suppression of classic PIM effectors and also elements of the mTOR pathway, suggesting interplay between PIM and mTOR signals. Our data demonstrate that PIM inhibition enhances the effects of imatinib mesylate on Ph+ leukemia cells. We also found that PIM inhibition results in suppression of leukemic cell proliferation and induction of apoptosis of Ph+ leukemia cells, including those resistant to imatinib mesylate. Importantly, inhibition of PIM results in enhanced suppression of primary leukemic progenitors from patients with CML. Altogether these findings suggest that pharmacological PIM targeting may provide a unique therapeutic approach for the treatment of Ph+ leukemias.

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