SIRT1-SIRT7 Expression in Patients with Lymphoproliferative Disorders Undergoing Hematopoietic Stem Cell Mobilization

SIMPLE SUMMARY: One of the treatment lines of patients with lymphoproliferative disorders is autologous transplantation, preceded by an effective mobilization of hematopoietic stem cells from the bone marrow niche into the peripheral blood. Sirtuins (SIRT1-SIRT7) are members of the NAD + -dependent class III histone deacetylase family, which affect the inflammatory response, hematopoiesis, angiogenesis, and the behavior of hematopoietic cells during mobilization and transplantation. In our work, we wanted to investigate how sirtuins expression changes on the day of the first apheresis as compared to the period before mobilization and how they can influence the efficacy of CD34+ cell collection. Our study revealed a significant increase in sirtuin expression on the day of the first apheresis as compared to the baseline. We demonstrated that the expression of SIRT5, SIRT6, and in particular SIRT7, on the day of first apheresis, may be associated with the efficacy of hematopoietic stem cell mobilization. ABSTRACT: Sirtuins are involved in the fate of hematopoietic stem cells (HSCs), including their metabolism, stress response, differentiation, migration, and apoptosis. The aim of this study was to explore SIRT1-7 expression during HSC mobilization. The study included 50 patients with lymphoproliferative disorders (39 multiple myeloma, 11 lymphoma). Samples were taken before mobilization (day 0) and on the day of first apheresis (day A). The sirtuin expression was evaluated by the Droplet Digital PCR (ddPCR) method. A significant increase of the SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 levels measured at day A as compared to baseline was observed. The study revealed a positive correlation between SIRT5, SIRT6, and SIRT7 expression and the CD34+ peak value in peripheral blood and the number of CD34+ cells collected on day A. Patients from the SIRT7 “high expressors” group collected more CD34+ cells on day A than “low expressors”. Upregulated expressions of SIRT3 and SIRT7 on the day of first apheresis were observed in patients in complete remission status (CR) as compared to the non-CR group. Our results suggest that the investigated sirtuins may influence the HSC migration and hematopoietic landscape during mobilization. SIRT5, SIRT6, and SIRT7 may be associated with the efficacy of HSC mobilization.