The impact of SAMHD1 expression and mutation status in mantle cell lymphoma: An analysis of the MCL Younger and Elderly trial.

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 =.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 =.65, P =.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. What's new? While mantle cell lymphoma (MCL) treatment has improved, relapse and unfavorable outcome remain problematic. Here, to better predict therapeutic response in MCL, the authors assessed the biomarker potential of the nucleotide metabolism enzyme SAMHD1. Analyses of patients in the MCL Younger and Elderly trial show that neither SAMHD1 protein expression nor mutation status are associated with failure‐free survival or complete remission rate upon cytarabine‐based treatment in MCL patients. Drug perturbation assays in B cell lymphoma cell lines suggest that high SAMHD1 expression mediates cytarabine resistance as monotherapy but not when combined with other chemotherapeutics, similar to MCL treatment in vivo. [ABSTRACT FROM AUTHOR]