Clinical and biological impact of SAMHD1 expression in mantle cell lymphoma

• Published in: Virchows Archiv : an international journal of pathology Vol. 480; no. 3; pp. 655 - 666
• Main Authors: Merrien, Magali, Wasik, Agata M., Ljung, Elin, Morsy, Mohammad H. A., de Matos Rodrigues, Joana, Carlsten, Mattias, Rassidakis, Georgios Z., Christensson, Birger, Kolstad, Arne, Jerkeman, Mats, Ek, Sara, Herold, Nikolas, Wahlin, Björn E., Sander, Birgitta
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2022; Springer Nature B.V
• Subjects: Acute myeloid leukemia; Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Autografts; Cell proliferation; Chemotherapy; Clinical Medicine; Correlation; Cytarabine; Cytarabine - pharmacology; Cytarabine - therapeutic use; Cytology; Hematologi; Hematology; Hematopoietic Stem Cell Transplantation - methods; Humans; Klinisk medicin; Leukemia; Lymphoma; Lymphoma, Mantle-Cell - drug therapy; Lymphoma, Mantle-Cell - genetics; Lymphoma, Mantle-Cell - pathology; Mantle cell lymphoma; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Metabolites; Original; Original Article; Pathology; Patients; Prognostic factors; SAM Domain and HD Domain-Containing Protein 1 - genetics; SAMHD1; siRNA; Stem cell transplantation; Stem cells; Transcription; Transplantation; Transplantation, Autologous; Tumor cells; Tumors; Cytarabine; SAMHD1; Prognostic factors; Mantle cell lymphoma
• ISSN: 0945-6317; 1432-2307; 1432-2307
• DOI: 10.1007/s00428-021-03228-w

SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) that restricts viral replication in infected cells and limits the sensitivity to cytarabine by hydrolysing its active metabolite, as recently shown in acute myeloid leukemia. Cytarabine is an essential component in the Nordic mantle cell lymphoma protocols (MCL2 and MCL3) for induction and high-dose chemotherapy treatment before autologous stem cell transplantation for younger patients with mantle cell lymphoma (MCL). We here investigated the expression of SAMHD1 in a population-based cohort of MCL ( N  = 150). SAMHD1 was highly variably expressed in MCL (range, 0.4% to 100% of positive tumor cells). Cases with blastoid/pleomorphic morphology had higher SAMHD1 expression ( P  = 0.028) and SAMHD1 was also correlated to tumor cell proliferation ( P  = 0.016). SAMHD1 expression showed moderate correlation to the expression of the transcriptional regulator SOX11 ( P  = 0.036) but genetic silencing of SOX11 and SAMHD1 by siRNA in MCL cell lines did not suggest mutual regulation. We hypothesized that expression of SAMHD1 could predict short time to progression in patients treated with Cytarabine as part of high-dose chemotherapy. Despite the correlation with known biological adverse prognostic factors, neither low or high SAMHD1 expression correlated to PFS or OS in patients treated according to the Nordic MCL2 or MCL3 protocols ( N  = 158).