Overexpression of NIMA related kinase 2 in multiple myeloma and its relevance with disease features and prognosis to bortezomib treatment.

WHAT IS KNOWN AND OBJECTIVE: NIMA related kinase 2 (NEK2) promotes the malignant transformation and enhances the chemoresistance to proteasome inhibitor in multiple myeloma (MM) cell lines. The current study aimed to further investigate its correlation with clinical features and responsiveness to bortezomib treatment in MM patients. METHODS: Totally, 76 MM patients and 30 health donors (HDs) were enrolled to collect bone marrow plasma cells for NEK2 detection using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Meanwhile, NEK2 siRNA was transfected into the RPMI-8226 and KMS-11 cells, subsequently their cell viability was evaluated using Cell Counting Kit-8 reagent after treatment with different doses of bortezomib. RESULTS AND DISCUSSION: NEK2 expression was higher in MM patients compared with HDs (Z = -5.123, p < 0.001). Besides, elevated NEK2 expression was associated with the occurrence of the bone lesion (χ2  = 4.610, p = 0.032) and t (4; 14) (χ2  = 3.971, p = 0.046). Additionally, elevated NEK2 expression was correlated with declined objective response rate (ORR) (χ2  = 4.808, p = 0.028), but not with complete response (CR) (χ2  = 2.341, p = 0.126). More importantly, elevated NEK2 expression was correlated with shorter progression-free survival (PFS) (χ2  = 8.352, p = 0.039), but not with overall survival (OS) (χ2  = 5.624, p = 0.131), What is more, NEK2 silence decreased the cell viability under bortezomib treatment and the inhibitory concentration (IC50 ) value of bortezomib in RPMI-8226 and KMS-11 cell lines (all p < 0.05). WHAT IS NEW AND CONCLUSION: NEK2 overexpression links with occurrence of bone lesion, t (4; 14), and poor prognosis to bortezomib treatment in MM patients.

Expression of Cysteine-Rich Secreted Acidic Protein in Multiple Myeloma and Its Effect on the Biological Behavior of Cancer Cells.

The multiple myeloma is a malignant clonal tumor of bone marrow plasma cells that is incurable and inevitably recurrent. The mechanisms of progression include tumor cell metastasis, immune escape, resistance to apoptosis, and malignant proliferation. The cysteine-rich secreted acidic protein is closely related to the growth, development, remodeling, and repair of cells and tissues. In our study, we divided myeloma patients and patients with other blood diseases into groups and measured the cysteine-rich secreted acidic protein (SPARC) content in the serum of different groups of patients as well as the prognostic differences. The U266 cells were transfected with interfering vectors and overexpressed SPARC vectors to determine the physiological functions of MM cells. Our results showed that SPARC was highly expressed in MM and the survival rate of the high SPARC expression group was lower than that of the low expression group. Interfering SPARC vectors inhibited cancer cell proliferation, migration, and invasion and promoted apoptosis. Overexpression of SPARC vectors promoted cancer cell development. SPARC affected the patient's disease development by regulating the biological behavior of the MM cells.