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Clinical and biological impact of SAMHD1 expression in mantle cell lymphoma

Merrien, Magali ; Wasik, Agata M. ; Ljung, Elin ; Morsy, Mohammad H.A. ; de Matos Rodrigues, Joana LU ; Carlsten, Mattias ; Rassidakis, Georgios Z. ; Christensson, Birger ; Kolstad, Arne and Jerkeman, Mats LU , et al. (2022) In Virchows Archiv 480(3). p.655-666
Abstract

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... (More)

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).

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cytarabine, Mantle cell lymphoma, Prognostic factors, SAMHD1
in
Virchows Archiv
volume
480
issue
3
pages
655 - 666
publisher
Springer
external identifiers
  • scopus:85118541440
  • pmid:34738194
ISSN
0945-6317
DOI
10.1007/s00428-021-03228-w
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021, The Author(s).
id
c4bd4d0e-c58d-4d0a-a6a1-3b2547c4250d
date added to LUP
2021-12-02 11:57:04
date last changed
2024-06-15 21:52:24
@article{c4bd4d0e-c58d-4d0a-a6a1-3b2547c4250d,
  abstract     = {{<p>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).</p>}},
  author       = {{Merrien, Magali and Wasik, Agata M. and Ljung, Elin and Morsy, Mohammad H.A. and de Matos Rodrigues, Joana and Carlsten, Mattias and Rassidakis, Georgios Z. and Christensson, Birger and Kolstad, Arne and Jerkeman, Mats and Ek, Sara and Herold, Nikolas and Wahlin, Björn E. and Sander, Birgitta}},
  issn         = {{0945-6317}},
  keywords     = {{Cytarabine; Mantle cell lymphoma; Prognostic factors; SAMHD1}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{655--666}},
  publisher    = {{Springer}},
  series       = {{Virchows Archiv}},
  title        = {{Clinical and biological impact of SAMHD1 expression in mantle cell lymphoma}},
  url          = {{http://dx.doi.org/10.1007/s00428-021-03228-w}},
  doi          = {{10.1007/s00428-021-03228-w}},
  volume       = {{480}},
  year         = {{2022}},
}