[The research on the expression and localization of multiple myeloma associated antigen MMSA-1].

AIM: To study the expression profile of multiple myeloma associated gene (MMSA-1), explore the relationship between its expression level and MM cells' proliferation as well as its celluler localization. METHODS: The mRNA levels of MMSA-1 and DKK1 genes were detected by RT-PCR in patients with MM, leukemia, non-tumor diseases and in the healthy donors, respectively. Then, their correlation was analyzed. The effects of Ibandronate Sodium on the cell cycle and early apoptosis of 8226 cells were analyzed by flow cytometry, and the effect on its protein expression was analyzed by immunohistochemistry. Construct MMSA-1 eukaryotic expression vector pCMV-Myc-MMSA-1, and antibody immunohistochemistry was applied to study the cellular localization of the protein. RESULTS: MMSA-1 gene was expressed in all of the specimens described above, and the mRNA level in MM was much higher than that in the others, just like DKK1 gene. More than that, their expression exhibited a significant positive correlation. Ibandronate Sodium could inhibit cell proliferation by a cell-cycle arrest in S-phase. By reducing cell maturation promoting factor release, it stopped the cell cycle, promoted their early apoptosis and decreased the protein expression of MMSA-1. MMSA-1 protein principally distributed on cell membranes, however, there are a small quantity in cytalplasm. CONCLUSION: These results revealed that MMSA-1 may play a pivotal role in MM proliferation and osteolysis destruction, which lay the foundation for the further study of biological function and immunotherapy based on MMSA-1.

Peptide-based immunotherapy for multiple myeloma: current approaches.

Multiple myeloma (MM) is a clonal B-cell malignancy with many fatal clinical sequelae. Despite extensive therapeutic approaches, cures remain rare exceptions. A recent promising area of investigation is the development of immunotherapeutic approaches that target and eliminate myeloma cells more selectively. Because of its potential to promote the destruction of cancerous cells via cytotoxic T-cell responses, peptide-based immunotherapy is one of these strategies to have attracted considerable attention. Furthermore, many studies were carried out to identify the best epitope peptides, the optimal vaccine formulation and schedule, and the preferable clinical situation for vaccination. Based on these results, various epitope peptides have been identified that may be selectively targeted by host immunity, and various approaches have been used to enhance the immune responses of peptides. This chapter focuses on reviewing previous immunotherapy trials, describing the current strategies for peptide-based immunotherapy, and discussing the achievable prospects in MM.

Involvement of oxidative stress in the relapse of acute myeloid leukemia.

The aims of the present study were to determine the level of oxidative stress and the salient factors leading to the relapse of acute myeloid leukemia (AML). Oxidative stress-related parameters and the expressions of specific genes were monitored in 102 cases of AML during a pretreatment period from a primary status to a relapse status. In addition, age-matched healthy subjects were classified as controls. The activities of adenosine deaminase and xanthine oxidase were higher in the relapse condition, whereas those of glutathione peroxidase, monoamine oxidase, and superoxide dismutase, and the total antioxidant capacity (T-AOC) were lower in the primary condition and in controls. Of particular note, levels of advanced oxidation protein products, malondialdehyde, and 8-hydroxydeoxyguanosine were also significantly higher in relapse patients. Furthermore, real-time PCR with SYBR Green revealed that the expression levels of human thioredoxin (TRX) and indoleamine 2,3-dioxygenase were increased in relapse patients. Pearson correlation analysis revealed that the T-AOC was positively correlated with GSH but negatively correlated with 8-OHdG, TRX, and indoleamine 2,3-dioxygenase. Linear regression showed that a low T-AOC and up-regulated TRX expression were the independent factors correlated with relapse. A strong association between oxidative stress and the incidence of disease relapse was observed, which has potential prognosis implications. These results indicate that oxidative stress is a crucial feature of AML and probably affects the development and relapse of AML.