Low Rap1-interacting factor 1 and sirtuin 6 expression predict poor outcome in radiotherapy-treated Hodgkin lymphoma patients
Bur, Hamid; Haapasaari, Kirsi-Maria; Turpeenniemi-Hujanen, Taina; Kuittinen, Outi; Auvinen, Päivi; Marin, Katja; Soini, Ylermi; Karihtala, Peeter (2017-08-08)
Hamid Bur, Kirsi-Maria Haapasaari, Taina Turpeenniemi-Hujanen, Outi Kuittinen, Päivi Auvinen, Katja Marin, Ylermi Soini & Peeter Karihtala (2018) Low Rap1-interacting factor 1 and sirtuin 6 expression predict poor outcome in radiotherapy-treated Hodgkin lymphoma patients, Leukemia & Lymphoma, 59:3, 679-689, DOI: 10.1080/10428194.2017.1344840
© Taylor & Francis 2018. This is an Accepted Manuscript of an article published by Taylor & Francis in Leukemia & Lymphoma on 8.8.2017, available online: https://doi.org/10.1080/10428194.2017.1344840.
https://rightsstatements.org/vocab/InC/1.0/
https://urn.fi/URN:NBN:fi-fe2019110136210
Tiivistelmä
Abstract
Sirtuins (SIRTs) are a family of histone deacetylases, which widely regulate cellular metabolism and are also involved in DNA repair. Rap1-interacting factor 1 (Rif1) and O⁶-alkylguanine DNA alkyltransferase (MGMT) are DNA-repair enzymes, which may potentially be involved in resistance to treatment of classical Hodgkin lymphoma (HL). We assessed the expression levels of (previously unstudied) SIRT1, SIRT4, SIRT6, Rif1, and MGMT immunohistochemically in 85 patients with untreated classical HL. Aberrant distributions of SIRT1, SIRT4, and SIRT6 were detected in Hodgkin neoplastic Reed–Sternberg (RS) cells compared with reactive elements. Low-level expression of both Rif1 and SIRT6 predicted dismal relapse-free survival in radiotherapy-treated patients (multivariate analysis; HR 8.521; 95% CI 1.714–42.358; p = .0088). Expression levels of SIRT1, 4, and 6 were abnormally distributed in RS cells, suggesting a putative role of aberrant acetylation in classical HL carcinogenesis. Rif1 and SIRT6 may also have substantial prognostic and even predictive roles in classical HL.
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