Aberrant expression and localization of the cytoskeleton-binding pp52 (LSP1) protein in hairy cell leukemia

Non-retractable cell surface projections and cytoskeleton-mediated function al defects are distinguishing features of both hairy cell leukemia (HCL) an d neutrophil actin dysfunction (NAD). These defects in NAD neutrophils are attributed to moderate over-expression of pp52 (LSP1), the F-actin-binding, leukocyte-specific phosphoprotein. Here we report that pp52 is similarly e levated in HCL patient PBMCs. Established HCL cell lines exhibited characte ristic morphological features like those of fresh HCL cells and showed elev ated pp52 levels. The excess pp52 in these HCL cell lines was selectively a ssociated with the F-actin-rich cytoskeletal arrays in surface projections. Treatments producing radical changes in HCL cell shape also altered pp52 e xpression and intracellular distribution. Alpha interferon (IFN alpha, used to treat HCL) reduced pp52 levels, normalized intracellular pp52 distribut ion and reverted HCL cells to rounded B cell morphology. Phorbol ester stim ulation rapidly generated hyper-phosphorylated pp52 isoforms which transloc ated from the cytoskeleton to the cytosol prior to the further elongation o f surface spikes. This indicates a direct role for phosphorylation in contr olling pp52 interactions with the cytoskeleton. Overall, these findings str ongly suggest that elevated pp52 expression and/or selective cytoskeletal a ssociation contributes to the distinctive morphology of HCL cells. (C) 2001 Elsevier Science Ltd. All rights reserved.