Peters, Tara L., Li, Lingxiao, Tula-Sanchez, Ana A., Pongtornpipat, Praechompoo and Schatz, Jonathan H. (2016) Control of Translational Activation by PIM Kinase in Activated B-Cell Diffuse Large B-Cell Lymphoma Confers Sensitivity to Inhibition by PIM447. Oncotarget, 7 (39). pp. 63362-63373. ISSN 1949-2553

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.

Item Type:	Article
Date Deposited:	12 Oct 2016 00:45
Last Modified:	12 Oct 2016 00:45
URI:	https://oak.novartis.com/id/eprint/30299