The AKT kinase is activated in multiple myeloma tumor cells

Immunohistochemistry (IHC) was performed on archived bone marrow (BM) with a phosphospecific anti-AKT antibody. IHC on 26 BM biopsies from patients wi th multiple myeloma (MM) demonstrated phospho-AKT staining of malignant pla sma cells in a cell membrane-specific pattern, whereas nonmalignant hematop oietic cells did not stain. Preabsorption of the antibody with phosphorylat ed AKT peptide, but not nonphosphorylated peptide, abrogated staining. Freq uency of plasma cell staining in BMs of patients with stage I or smoldering MM was significantly less than that of stage III MM marrows. Plasma cells in 10 patients with monoclonal gammopathy of undetermined significance were not stained by the antibody. To investigate the significance of AKT activa tion, 2 cell lines initiated from cultures of primary MM cells were also st udied. Both demonstrated constitutive AKT activation. Interruption of AKT a ctivation and activity, achieved by either exposure to wortmannin or by ect opic expression of a dominant negative AKT mutant, resulted in inhibition o f MM cell growth in vitro. These results indicate that activation of the AK T kinase is a characteristic of MM cells and suggest that AKT activity is i mportant for MM cell expansion. (C) 2001 by The American Society of Hematol ogy.