Abstract B269: Effects of blocking aberrantly expressed CSF-1R in Hodgkin lymphoma.

Abstract

Abstract The human genome contains a large number of repetitive elements that have been suspected to play a role in human diseases. Recent literature has shown that aberrant activation of one of these repetitive elements, a long terminal repeat (LTR), leads to lineage inappropriate expression of the CSF-1 receptor (CSF-1R) transcript in Hodgkin's lymphoma (HL) clinical samples and cell lines. CSF1-R, also known as Feline McDonough Sarcoma (FMS), is the receptor for CSF-1 and IL-34, and under normal circumstances it plays an important role in monocyte survival, proliferation, and differentiation as well as osteoclast generation. Aberrant expression of CSF-1R has been shown previously to support proliferation and survival in HL cells. To confirm the role of CSF-1R in HL, we determined that 17 of 17 HL clinical samples and 7 of 7 HL cell lines were positive for the aberrant CSF-1R transcript by TaqMan and traditional PCR, while non-HL cell lines were negative for the aberrant CSF-1R transcript. The HL lines were further characterized for surface expression of CSF-1R by flow cytometry and CSF-1 secretion by ELISA. L-1236 cells expressed the highest levels of CSF-1R and CSF-1. Treatment of the HL cell lines with CSF-1R-Fc, resulted in reduced viability in four of the five lines, consistent with the hypothesis that HL cell lines are sensitive to CSF-1 as a growth factor. Additionally, it was found that treating the L-1236 HL cell line with the CSF-1R small molecule inhibitor JNJ-40646527 had a significant effect on viability of the HL cell line L-1236, with an IC50 of 264 nM at 72 hrs. JNJ-40646527 did not have a significant effect on the viability of several other HL cell lines. These results indicate that aberrant LTR driven CSF-1R expression may play a role in the pathogenesis of Hodgkin's lymphoma (HL) and could be a potential target for Hodgkin's lymphoma therapy. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B269. Citation Format: Liam Campion, Nikki Deangelis, Catherine Ferrante, Raluca Verona, Shobha Seetharam, Carl Manthey, Linda Snyder. Effects of blocking aberrantly expressed CSF-1R in Hodgkin lymphoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B269.