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Blood, 1 November 2001, Vol. 98, No. 9, pp. 2853-2855
BRIEF REPORT
The AKT kinase is activated in multiple myeloma tumor
cells
Jung-hsin Hsu,
Yijiang Shi,
Stanislaw Krajewski,
Stephen Renner,
Myrna Fisher,
John C. Reed,
Thomas F. Franke, and
Alan Lichtenstein
From the Department of Medicine and Pathology, West Los
Angeles Veterans Administration Medical Center and Jonsson
Comprehensive Cancer Center, Los Angeles, CA; Burnham Institute, La
Jolla, CA; and the Department of Pharmacology, Columbia University, New
York, NY.
Immunohistochemistry (IHC) was performed on archived bone
marrow (BM) with a phosphospecific anti-AKT antibody. IHC on 26 BM
biopsies from patients with multiple myeloma (MM) demonstrated phospho-AKT staining of malignant plasma cells in a cell
membrane-specific pattern, whereas nonmalignant hematopoietic cells
did not stain. Preabsorption of the antibody with phosphorylated AKT
peptide, but not nonphosphorylated peptide, abrogated staining.
Frequency 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 activation, 2 cell lines initiated from cultures of
primary MM cells were also studied. Both demonstrated constitutive AKT
activation. Interruption of AKT activation and activity, achieved by
either exposure to wortmannin or by ectopic expression of a dominant
negative AKT mutant, resulted in inhibition of MM cell growth in vitro.
These results indicate that activation of the AKT kinase is a
characteristic of MM cells and suggest that AKT activity is important
for MM cell expansion.

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