Abstract 4974: IL-1 receptor-associated kinase-1 and -4 expression in Hodgkin lymphoma

Abstract

Abstract BACKGROUND: The Toll-like receptor (TLR) mediates nuclear factor kappa B (NFkB) activation in lymphocytes using a family of intermediary proteins called IL-1 receptor associated kinase (IRAK). Mutations within and upregulation of this pathway have been described in the carcinogenesis of non-Hodgkin lymphoma (NHL), but it is not known whether IRAK proteins are present in Hodgkin lymphoma (HL). Furthermore, Epstein-Barr virus (EBV) has been shown to activate NFkB in HL but its association with proteins upstream of NFkB is not described. METHODS: 1. We performed Western blots on two Hodgkin Reed-Sternberg (HRS) cell lines to detect total IRAK-1 and -4, and phospho-IRAK-1 and -4 (the activated forms). 2. Archived lymph node biopsy samples from Hodgkin lymphoma patients diagnosed at the University of Maryland were stained for IRAK-4. RESULTS: 1. IRAK-1, IRAK-4, p-IRAK-1 and p-IRAK-4 were present in the malignant HRS cells in two HRS cell lines (HDLM-2 and KM-H2). 2. Seventeen lymph node biopsy samples showed marked positivity for IRAK-4 (mean of 2.3 on a 0-4 scale), as well as lesser positivity in surrounding reactive lymphocytes and histiocytes (mean of 1.6). The only sample to achieve a staining level of 4 was of mixed cellularity subtype, and was EBER-positive and HIV-negative. CONCLUSIONS: The IRAK proteins are present in the malignant HRS cells of Hodgkin lymphoma. Further work will examine IRAK-1, and phospho-IRAK-1 and -4 in the lymph node samples. Future studies should also examine whether IRAK causes downstream NFkB activation in HL as it does in NHL, and whether HRS cells depend on IRAK's presence for survival. A possible association with EBV infection will also be investigated. IRAK is a targetable protein with inhibitors available, so this and future studies may reveal new therapeutic strategies in relapsed Hodgkin lymphoma. Citation Format: Victoria S. Giffi, Kenisha M. Younger, Zeba Singh, Qing Chen, Eduardo Davila, Amy S. Kimball. IL-1 receptor-associated kinase-1 and -4 expression in Hodgkin lymphoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4974. doi:10.1158/1538-7445.AM2015-4974