p16(INK4a) and p15(INK4b) gene methylations in plasma cells from monoclonal gammopathy of undetermined significance

p15(INK4b) and p16(INK4a) proteins are cell cycle regulators involved in th e inhibition of G1 phase progression. High frequency of methylation of both genes has been reported in multiple myeloma (MM), but it remains to be det ermined how and when these alterations contribute to tumorigenesis. Monoclo nal gammopathy of undetermined significance (MGUS) represents an early dise ase stage in a fraction of MMs. Plasma cells from 33 patients with MGUS and 33 patients with NIM were isolated and analyzed for p15(INK4b) and p16(INK 4a) methylation by methylation-specific polymerase chain reaction. Selectiv e methylation was found in 19% for p16(INK4a), 36% for p15(INK4b), and 6.5% for both genes in MGUS, and frequencies were similar in MM suggesting that methylation of these genes is an early event, not associated with transiti on from MGUS to NIM. p15(INK4b) and p16(INK4a) gene methylation might contr ibute to immortalization of plasma cells rather than malignant transformati on in the natural history of MM. (C) 2001 by The American Society of Hemato logy.