Figure 3. NEK2 activates the canonical NF-κB signaling pathway.

(A) Affymetrix gene expression profiling data from 351 purified bone marrow plasma cell populations in the Total Therapy 2 (TT2) cohort was used to correlate the expression of NEK2 with the NF-κB signaling score. Pearson’s correlation was performed between log₂ [NEK2 signal] and the NF-κB signaling score. (B) H1299 cells were transfected with luciferase vector under a p65-dependent promoter, an internal Renilla control vector, p52 as a negative control, or a NEK2-OE vector. Results show that NEK2 overexpression increased the luciferase signal 2.5-fold compared with p52. (C) An unsupervised hierarchical cluster analysis was used to classify 351 multiple myeloma samples using NEK2 and 31 NF-κB genes regulated by NEK2. (D–G) Kaplan-Meier analyses show event-free survival (EFS) and overall survival (OS) of multiple myeloma patients enrolled in TT2 (D and E) and HOVON-65 (F and G) cohorts. Each line represents different subgroups identified in C and is described in the figure and color coded.