KML001 reduced the growth of all MM cell lines examined with an IC50 of 5x10‑8 M. Exposure to KML001 (5x10‑8 M) decreased levels of cyclins A/B1/D1/E1, CDK2/4/6 in U266 cells and increased the p21 and p27 levels.
Mechanistically, lenalidomide plus dexamethasone synergistically induced expression of the tumor suppressor genes Egr1, Egr2, Egr3, p15, p21, and p27 in MM cell lines and MM patient cells.
In this study we show, in growing mouse hybridoma (7TD1) and human myeloma (U266) cell lines, that p27 is highly expressed but slightly upregulated when cells are arrested, regardless to the phases of the cell cycle.