The Involvement of LAG-3positive Plasma Cells in the Development of Multiple Myeloma.

The Lymphocyte-Activation Protein 3 (LAG-3) inhibitory receptor is expressed on regulatory plasma cells (PCs). Micro-environmental cells that express LAG-3 were found to be increased during the progression of smoldering multiple myeloma (SMM). To assess the possible role of LAG-3 expression on regulatory PCs in patients with plasma cell dyscrasia. Purified Cluster of Differentiation 138 (CD138+) PCs from patients with premalignant conditions, active multiple myeloma (MM), and controls were analyzed for the expression of LAG-3 by flow cytometry. Autologous CD8+T cells were incubated with sorted LAG-3pos or LAG-3neg PCs for 24 h. The expression of granzyme (Grz) in CD8+T cells was assessed by flow cytometry. LAG-3 expression on PCs in active MM (newly diagnosed and relapse refractory MM) was significantly increased compared to monoclonal gammopathy of undetermined significance (MGUS)/ SMM. Grz expression was significantly decreased in CD8+T cells incubated with CD138+LAG-3pos PCs, compared to CD138+LAG-3neg PCs in patients with plasma cell dyscrasia, n = 31, p = 0.0041. LAG-3 expression on malignant PCs can be involved in the development of MM from MGUS by decreasing the expression of Grz in CD8+T cells.

Peripheral Blood Cell Mitochondrial Dysfunction in Myelodysplastic Syndrome Can Be Improved by a Combination of Coenzyme Q10 and Carnitine.

Structural mitochondrial abnormalities and genetic aberrations in mitochondrial proteins have been known in Myelodysplastic syndrome (MDS), yet there is currently little data regarding MDS's metabolic properties and energy production cells. In the current study, we used state-of-the-art methods to assess OXPHOS in peripheral blood cells obtained from MDS patients and healthy controls. We then assessed the effect of food supplements-Coenzyme Q10 and carnitine on mitochondrial function and hematological response. We show here for the first time that there is a significant impairment of mitochondrial respiration in peripheral blood cells in low-risk MDS, which can be improved with food supplements. We also show that these supplements may improve the cytopenia and quality of life.