Pre-clinical evidence of PIM kinase inhibitor activity in BCR-ABL1 unmutated and mutated Philadelphia Chromosome Ph (+) -Positive Leukemias

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

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)33206-33216
Number of pages11
JournalOncotarget
Volume6
Issue number32
DOIs
StatePublished - 2015

Keywords

  • CML
  • MTOR signaling
  • PIM kinase
  • Philadelphia chromosome-positive leukemia

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Pre-clinical evidence of PIM kinase inhibitor activity in BCR-ABL1 unmutated and mutated Philadelphia Chromosome Ph (+) -Positive Leukemias'. Together they form a unique fingerprint.

  • Cite this