Work

NEK2 induces osteoclast differentiation and bone destruction via heparanase in multiple myeloma

Year: 2017

Type: article

Abstract: To positively modulate multiple myeloma (MM) bone disease, understanding the mechanism of bone destruction is required to provide better targeted therapy. Specific molecular genetic lesions and tumor cell–stroma interactions influence the clinical course and response to therapy, all of which can vary markedly. 1 , 2 Our recent study demonstrates that an increased chromosomal instability (CIN) signature is associated with drug resistance and poor prognosis. 3 , 4 High expression of NEK2, one of the CIN genes, has been shown to induce premature splitting of centrosomes, while suppression of NEK2 blocks spindle and chromosome segregation, resulting in accumulation of multiple centrosomes. 5 , 6 Interestingly, we found that NEK2 expression is highly correlated with the expression of Heparanase 1 (HPSE), and its expression is significantly increased in the few myeloma cells still present in complete remission and not unexpectedly also in relapse. 3 Although the tumor cell number is markedly decreased in remission patients, bone osteolysis still continues, suggesting that drug-resistant MM cells with high expression of NEK2 and HPSE, may play a critical role in bone destruction or prevent the repair of bone disease during remission.

Source: Leukemia

DOI: 10.1038/leu.2017.115