Abstract
Non-retractable cell surface projections and cytoskeleton-mediated functional defects are distinguishing features of both hairy cell leukemia (HCL) and 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 elevated in HCL patient PBMCs. Established HCL cell lines exhibited characteristic morphological features like those of fresh HCL cells and showed elevated pp52 levels. The excess pp52 in these HCL cell lines was selectively associated with the F-actin-rich cytoskeletal arrays in surface projections. Treatments producing radical changes in HCL cell shape also altered pp52 expression and intracellular distribution. Alpha interferon (IFNα, used to treat HCL) reduced pp52 levels, normalized intracellular pp52 distribution and reverted HCL cells to rounded B cell morphology. Phorbol ester stimulation rapidly generated hyper-phosphorylated pp52 isoforms which translocated from the cytoskeleton to the cytosol prior to the further elongation of surface spikes. This indicates a direct role for phosphorylation in controlling pp52 interactions with the cytoskeleton. Overall, these findings strongly suggest that elevated pp52 expression and/or selective cytoskeletal association contributes to the distinctive morphology of HCL cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 57-67 |
| Number of pages | 11 |
| Journal | Leukemia Research |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2001 |
Funding
This work was funded by the NIH Grants; GM40185, CA85841, AI20069, AI33085 and AI19884. E.K.M. was funded by the UC Office of the President Fellowship, the UCLA Cota-Robles Fellowship, the NIH Pre-doctoral Institutional Training Grant CA09120, and the UC Dissertation Year Fellowship. The authors would like to thank Dr M. Taylor and Dr C.H. Uittenbogaart for the HCL cell lines used in this study and Amgen for their generous contribution of IFNα. Special thanks to Dr C.S. Malone for her statistical expertise. Thanks to Dr J. Braun, Dr S.A. Omori, Dr M.S. Gordon, Dr W.J. Wood, Jr, Dr J. Perry and Dr J.T. Kadonaga for technical advice and helpful discussions. We acknowledge Jeffrey Chun and James J. Chang for technical assistance. E.K. Miyoshi contributed to the collection, assembly and analysis of data, provided concept and design, drafted and revised the paper and gave full approval. P.L. Stewart and M.B. Lee contributed to the data collection and technical support. A.A. Thompson contributed to the collection and assembly of data, and provided study materials and concept and design. P.W. Kincade provided funding, study materials, and critical revisions. R. Wall provided concept and design, study materials, data analysis, critical revisions, funding, administrative support and gave final approval.
Keywords
- Cell size
- Hairy cell
- LSP1
- Leukemia
- Leukocytes
- Microfilament protein
- Phosphoproteins
- pp52
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research
