Clinical and biological impact of SAMHD1 expression in mantle cell lymphoma.

Autor: Merrien M; Department of Laboratory Medicine, Div. of Pathology, Karolinska Institutet and Karolinska University Hospital, SE14186, Stockholm, Sweden., Wasik AM; Department of Laboratory Medicine, Div. of Pathology, Karolinska Institutet and Karolinska University Hospital, SE14186, Stockholm, Sweden., Ljung E; Department of Pathology, Karolinska University Hospital, Solna, Sweden., Morsy MHA; Department of Laboratory Medicine, Div. of Pathology, Karolinska Institutet and Karolinska University Hospital, SE14186, Stockholm, Sweden., de Matos Rodrigues J; Department of Immunotechnology, Lund University, Lund, Sweden., Carlsten M; PO Haematology and Unit of Haematology, Department of Medicine at Huddinge, Karolinska University Hospital and Karolinska Institutet, Solna, Sweden.; Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Solna, Sweden., Rassidakis GZ; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Christensson B; Department of Laboratory Medicine, Div. of Pathology, Karolinska Institutet and Karolinska University Hospital, SE14186, Stockholm, Sweden., Kolstad A; Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway., Jerkeman M; Department of Oncology, Lund University, Lund, Sweden., Ek S; Department of Immunotechnology, Lund University, Lund, Sweden., Herold N; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.; Paediatric Oncology, Astrid Lindgren Children's Hospital, Karolinska University Hospital Solna, Solna, Sweden., Wahlin BE; PO Haematology and Unit of Haematology, Department of Medicine at Huddinge, Karolinska University Hospital and Karolinska Institutet, Solna, Sweden., Sander B; Department of Laboratory Medicine, Div. of Pathology, Karolinska Institutet and Karolinska University Hospital, SE14186, Stockholm, Sweden. birgitta.sander@ki.se.
Jazyk: angličtina
Zdroj: Virchows Archiv : an international journal of pathology [Virchows Arch] 2022 Mar; Vol. 480 (3), pp. 655-666. Date of Electronic Publication: 2021 Nov 04.
DOI: 10.1007/s00428-021-03228-w
Abstrakt: 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).
(© 2021. The Author(s).)
Databáze: MEDLINE
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