Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447

Tara L. Peters, Lingxiao Li, Ana A. Tula-Sanchez, Praechompoo Pongtornpipat, Jonathan H Schatz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The PIM family kinases promote growth and survival of tumor cells and are expressed in a wide variety of human cancers. Their potential as therapeutic targets, however, is complicated by overlapping activities with multiple other pathways and remains poorly defined in most clinical scenarios. Here we explore activity of the new pan-PIM inhibitor PIM447 in a variety of lymphoid-derived tumors. We find strong activity in cell lines derived from the activated B-cell subtype of diffuse large B-cell lymphoma (ABC-DLBCL). Sensitive lines show lost activation of the mTORC1 signaling complex and subsequent lost activation of cap-dependent protein translation. In addition, we characterize recurrent PIM1 protein-coding mutations found in DLBCL clinical samples and find most preserve the wild-type protein's ability to protect cells from apoptosis but do not bypass activity of PIM447. Pan-PIM inhibition therefore may have an important role to play in the therapy of selected ABC-DLBCL cases.

Original languageEnglish (US)
Pages (from-to)63362-63373
Number of pages12
JournalOncotarget
Volume7
Issue number39
DOIs
StatePublished - 2016
Externally publishedYes

Fingerprint

Lymphoma, Large B-Cell, Diffuse
B-Lymphocytes
Phosphotransferases
Play Therapy
Neoplasms
Aptitude
Protein Biosynthesis
Cell Survival
Proteins
Apoptosis
Cell Line
Mutation
Growth
Inhibition (Psychology)
Therapeutics

Keywords

  • ABC-DLBCL
  • B-cell receptor signaling
  • Cap-Dependent Translation
  • Lymphomagenesis
  • PIM kinase

ASJC Scopus subject areas

  • Oncology

Cite this

Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447. / Peters, Tara L.; Li, Lingxiao; Tula-Sanchez, Ana A.; Pongtornpipat, Praechompoo; Schatz, Jonathan H.

In: Oncotarget, Vol. 7, No. 39, 2016, p. 63362-63373.

Research output: Contribution to journalArticle

Peters, Tara L. ; Li, Lingxiao ; Tula-Sanchez, Ana A. ; Pongtornpipat, Praechompoo ; Schatz, Jonathan H. / Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447. In: Oncotarget. 2016 ; Vol. 7, No. 39. pp. 63362-63373.
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