University of Oulu

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

Low Rap1-interacting factor 1 and sirtuin 6 expression predict poor outcome in radiotherapy-treated Hodgkin lymphoma patients

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Author: Bur, Hamid1; Haapasaari, Kirsi-Maria2; Turpeenniemi-Hujanen, Taina1;
Organizations: 1Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and Cancer and Translational Medicine Research Unit, University of Oulu, Finland
2Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland
3Department of Oncology, Cancer Center, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
4Department of Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland, Cancer Center of Eastern Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
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Language: English
Published: Informa, 2018
Publish Date: 2019-11-01


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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Series: Leukemia & lymphoma
ISSN: 1042-8194
ISSN-E: 1029-2403
ISSN-L: 1042-8194
Volume: 59
Issue: 3
Pages: 679 - 689
DOI: 10.1080/10428194.2017.1344840
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
3122 Cancers
Funding: Finnish Anti-Tuberculosis Foundation 10.13039/501100008368 Väisänen Fund 622014 Cancer Foundation Finland 160122/2016 This study was supported by the Finnish Anti-Tuberculosis Association under Grant [2016], Väisänen Fund in Terttu-Foundation under Grant (622014), and the Cancer Foundation Finland under Grant [160122/2016].
Copyright information: © Taylor & Francis 2018. This is an Accepted Manuscript of an article published by Taylor & Francis in Leukemia & Lymphoma on 8.8.2017, available online: