Impact of global and gene-specific DNA methylation pattern in relapsed multiple myeloma patients treated with bortezomib

We studied seventy-five patients with relapsed MM treated with bortezomib-based regimens. DNA was isolated from bone marrow samples at the time of relapse. Global methylation was determined by ELISA, and CpG island DNA methylation profile of 30 genes by a DNA methylation PCR system. Patients with more than 3.95% of total DNA methylated achieved better overall survival (OS) (p = 0.004). A relatively low methylation percentage (<1.07%) of NFKB1 was also associated with longer OS after bortezomib treatment (p = 0.015). The combination of highly methylated global genome with low NFKB1 methylation status defined a specific subset of patients with better prognosis.