Expression, adverse prognostic significance and therapeutic small molecule inhibition of Polo-like kinase 1 in multiple myeloma

The amplified myeloma centrosome has been identified as a therapeutic target. The present study explored the expression and prognostic significance of the centrosome-associated protein PLK1 in myeloma and the effect of BI 2536, a potent and selective inhibitor of PLK1, on myeloma cells. High plasma cell expression of PLK1 protein in myeloma patient bone marrow biopsies is an independent adverse prognostic factor (HR = 2.3, p = 0.003 unadjusted; HR = 1.9, p = 0.03 in multivariable model). BI 2536 inhibits myeloma cell lines at nanomolar concentrations, and is therapeutic for xenografts in NOD/SCID mice. PLK1 inhibition is a potential new strategy for the treatment of multiple myeloma.

► We show that increased PLK1 expression in multiple myeloma is a poor prognostic factor.
► The PLK1 inhibitor BI 2536 is toxic to myeloma cell lines and murine myeloma xenografts.
► Further exploration of PLK1 as a therapeutic target in myeloma is warranted.