TY - JOUR
T1 - The impact of SAMHD1 expression and mutation status in mantle cell lymphoma: An analysis of the MCL Younger and Elderly trial
AU - Roider, Tobias
AU - Wang, Xi
AU - Hüttl, Katrin
AU - Müller-Tidow, Carsten
AU - Klapper, Wolfram
AU - Rosenwald, Andreas
AU - Stewart, James Peter
AU - Gonzalez de Castro, David
AU - Dreger, Peter
AU - Hermine, Olivier
AU - Kluin-Nelemans, Hanneke C
AU - Grabe, Niels
AU - Dreyling, Martin
AU - Pott, Christiane
AU - Ott, German
AU - Hoster, Eva
AU - Dietrich, Sascha
N1 - This article is protected by copyright. All rights reserved.
PY - 2020/8/15
Y1 - 2020/8/15
N2 - The sterile alpha motif and histidine-aspartic domain-containing protein 1 (SAMHD1) has been demonstrated to predict the response to high-dose cytarabine consolidation treatment in acute myeloid leukemia patients. Here, we evaluated SAMHD1 as potential biomarker for the response to high-dose cytarabine in mantle cell lymphoma (MCL) patients. We quantified SAMHD1 protein expression and determined the mutation status in patients of the MCL Younger and Elderly trials (n = 189), who had received high-dose cytarabine- or fludarabine-based polychemotherapy. Additionally, we quantified SAMHD1 expression in B cell lymphoma cell lines and exposed them to cytarabine, fludarabine, and clinically relevant combinations. Across both trials investigated, SAMHD1 mutations had a frequency of 7.1 % (n = 13) and did not significantly affect the failure-free survival (FFS, p = 0.47). In patients treated with high-dose cytarabine- or fludarabine-containing regimes, SAMHD1 expression was not significantly associated with FFS or complete remission rate. SAMHD1 expression in B cell lymphoma cell lines, however, inversely correlated with their in vitro response to cytarabine as single agent (R = 0.65, p = 0.0065). This correlation could be reversed by combining cytarabine with other chemotherapeutics, such as oxaliplatin and vincristine, similar to the treatment regime of the MCL Younger trial. We conclude that this might explain why we did not observe a significant association between SAMHD1 protein expression and the outcome of MCL patients upon cytarabine-based treatment. This article is protected by copyright. All rights reserved.
AB - The sterile alpha motif and histidine-aspartic domain-containing protein 1 (SAMHD1) has been demonstrated to predict the response to high-dose cytarabine consolidation treatment in acute myeloid leukemia patients. Here, we evaluated SAMHD1 as potential biomarker for the response to high-dose cytarabine in mantle cell lymphoma (MCL) patients. We quantified SAMHD1 protein expression and determined the mutation status in patients of the MCL Younger and Elderly trials (n = 189), who had received high-dose cytarabine- or fludarabine-based polychemotherapy. Additionally, we quantified SAMHD1 expression in B cell lymphoma cell lines and exposed them to cytarabine, fludarabine, and clinically relevant combinations. Across both trials investigated, SAMHD1 mutations had a frequency of 7.1 % (n = 13) and did not significantly affect the failure-free survival (FFS, p = 0.47). In patients treated with high-dose cytarabine- or fludarabine-containing regimes, SAMHD1 expression was not significantly associated with FFS or complete remission rate. SAMHD1 expression in B cell lymphoma cell lines, however, inversely correlated with their in vitro response to cytarabine as single agent (R = 0.65, p = 0.0065). This correlation could be reversed by combining cytarabine with other chemotherapeutics, such as oxaliplatin and vincristine, similar to the treatment regime of the MCL Younger trial. We conclude that this might explain why we did not observe a significant association between SAMHD1 protein expression and the outcome of MCL patients upon cytarabine-based treatment. This article is protected by copyright. All rights reserved.
U2 - 10.1002/ijc.33202
DO - 10.1002/ijc.33202
M3 - Article
C2 - 32638373
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
ER -