Key Points
• Source: Virchows Archiv
• Conclusion/Relevance: “In conclusion, we here report a wide variability in SAMHD1 expression in MCL [mantle cell lymphoma] and a positive correlation to known biological adverse factors such as high tumor cell proliferation and blastoid/pleomorphic subtypes. However, neither low or high SAMHD1 expression correlated to OS or PFS in patients treated according to the Nordic MCL2 or MCL3 protocols.”
• Researchers assessed the expression of SAMHD1 in MCL vs non-malignant mantle zone B cells. They found that expression in normal mantle zone was about 30% positive cells. A bimodal expression pattern was observed in MCL, with one third of cases harboring fewer than 20% positive cells and half of the cases demonstrating more than half SAMHD1 positive cells.
• The authors observed a limited association between SAMHD1 and SOX11 protein expression in SOX11 positive MCL. Consequently using MCL cell lines, they examined whether the downregulation of one of these genes could impact expression levels of the other gene. By doing so, the noted that that SAMHD1 and SOX11 levels mutually regulate protein expression levels.
• They hypothesized that because SAMHD1 limits cytarabine efficacy via hydrolyzing the active metabolite, Ara-CTP, cases with a high number of SAMHD1 expressing cells exhibit decreased sensitivity to this constituent of therapy in a matter similar to acute myeloid leukemia.
• “Indeed, high SAMHD1 expression in B cell lymphoma cell lines confer resistance to cytarabine in vitro,” wrote the authors. “Cytarabine is however not enough as a single chemotherapy in high risk MCL and the combination treatment given in the MCL2 and MCL3 protocols could explain the lack of significant association between SAMHD1 expression and PFS or OS as here reported by us and recently also by others.”
• SAMHD1 is thought to exhibit tumor suppressor activity. It is a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) that limits viral replication in infected cells, as well as attenuating sensitivity to cytarabine by hydrolyzing its active metabolite. This effect was noted recently in acute myeloid leukemia. Importantly, in younger patients with MCL, cytarabine is an essential component in the Nordic mantle cell lymphoma protocols (MCL2 and MCL3) and contributes to induction and high-dose chemotherapy treatment before the administration of autologous stem cell transplantation.