CDKN2A and plasma cell myeloma: In contrast to the senescence of microenvironment cells, the senescence of myeloma cells is considered to be a protective mechanism against tumorigenesis.251 Indeed, our preliminary data obtained from patients with SMM showed that the level of the senescence marker gene CDKN2A was decreased in myeloma cells from SMM patients but increased in nonmyeloma cells (Fig. 7), consistent with previous literature reports.245–250 Interestingly, we and others135,252 have reported that the majority of senescent cells in long bones and fracture calluses in aged mice are of the osteolineage.