[Effect of Myeloma-Derived Exosomes on Surface Activating Receptors of NK Cells].

OBJECTIVE: To investigate the effect of myeloma-derived exosomes on surface activating receptors of NK cells, and to explore the mechanism of the function defect of NK cells. METHODS: The exosomes from the supernatant of multiple myeloma cell lines RPMI8226 and U266 were extracted by ultracentrifugation, and the size of them was identified under electron microscope; the human primary NK cells were extracted, and were co-cultured with the myeloma-derived exosomes (40 µg/ml), then the expression levels of surface activating receptors NKp46, NKp30 and NKG2D of NK cells at 0,1,4 and 24 hours were detected by flow cytometry. RESULTS: The exosomes showed small vesicular, sized 30-100 nm under electron microscope. The expression of surface activating receptors of NK cells declined at different degree after co-cultured with myeloma-derived exosomes. CONCLUSION: Myeloma-derived exosomes can inhibit the expression of surface activating receptors of NK cells.

Co-treatment of THP-1 cells with naringenin and curcumin induces cell cycle arrest and apoptosis via numerous pathways.

Acute myeloid leukemia (AML) is a hematological malignancy with a low survival rate. Curcumin, which is a multi-targeted anticancer agent, has been shown to exert anti­oxidant, anti­inflammatory, anti­mutagenic and anti­carcinogenic activities. Naringenin is extracted from citrus fruits and exerts anti­mutagenic and anti­carcinogenic activities in various types of cancer cells. However, the effects of curcumin and naringenin in combination in AML cells have yet to be studied. The present study aimed to investigate the combination effects of curcumin and naringenin on the viability, cell cycle distribution and apoptosis rate of THP­1 cells using cell viability assays, flow cytometry, and western blotting. Naringenin enhanced curcumin­induced apoptosis and cell viability inhibition. In addition, curcumin and naringenin induced cell cycle arrest at S phase and G2/M phase. Numerous pathways, including p53, c­Jun N­terminal kinases (JNK), Akt and extracellular signal­regulated kinases (ERK)1/2 pathways were markedly altered following treatment of THP­1 cells with curcumin and naringenin. These results indicated that naringenin may enhance curcumin­induced apoptosis through inhibiting the Akt and ERK pathways, and promoting the JNK and p53 pathways.

Construction of protein profile classification model and screening of proteomic signature of acute leukemia.

The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI_TOF_MS). The patients with acute leukemia were analyzed as unitary by the profiling that were grouped into acute promyelocytic leukemia (APL), acute myeloid leukemia-granulocytic (AML-Gran), acute myeloid leukemia-monocytic (AML-Mon) acute lymphocytic leukemia (ALL), and control. Based on 109 proteomic signatures, the classification models of acute leukemia were constructed to screen the predictors by the improvement of the proteomic signatures and to detect their expression characteristics. According to the improvement and the expression characteristics of the predictors, the proteomic signatures (M3829, M1593, M2121, M2536, M1016) characterized successively each group (CON, APL, AML-Gra, AML-Mon, ALL) were screened as target molecules for identification. Meanwhile, the proteomic-based class of determinant samples could be made by the classification models. The credibility of the proteomic-based classification passed the evaluation of Biomarker Patterns Software 5.0 (BPS 5.0) scoring and validated application in clinical practice. The results suggested that the proteomic signatures characterized by different blasts were potential for developing new treatment and monitoring approaches of leukemia blasts. Moreover, the classification model was potential in serving as new diagnose approach of leukemia.