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| Content Provider | PubMed Central |
|---|---|
| Author | Christensen, Dale J. Chen, Youwei Oddo, Jessica Matta, Karen M. Neil, Jessica Davis, Evan D. Volkheimer, Alicia D. Lanasa, Mark C. Friedman, Daphne R. Goodman, Barbara K. Gockerman, Jon P. Diehl, Louis F. Castro, Carlos M. De Moore, Joseph O. Vitek, Michael P. Weinberg, J. Brice |
| Copyright Year | 2011 |
| Abstract | B-cell chronic lymphocytic leukemia (CLL), an incurable leukemia, is characterized by defective apoptosis. We found that the SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A) tumor suppressor, is overexpressed in primary CLL cells and B-cell non-Hodgkin lymphoma (NHL) cell line cells. In CLL, increased levels of SET correlated significantly with disease severity (shorter time to treatment and overall survival). We developed SET antagonist peptides that bound SET, increased cellular PP2A activity, decreased Mcl-1 expression, and displayed selective cytotoxicity for CLL and NHL cells in vitro. In addition, shRNA for SET was cytotoxic for NHL cells in vitro. The SET antagonist peptide COG449 inhibited growth of NHL tumor xenografts in mice. These data demonstrate that SET is a new treatment target in B-cell malignancies and that SET antagonists represent novel agents for treatment of CLL and NHL. |
| Related Links | http://dx.doi.org/10.1182/blood-2011-04-351072 |
| Ending Page | 4158 |
| Page Count | 9 |
| Starting Page | 4150 |
| File Format | |
| ISSN | 00064971 |
| e-ISSN | 15280020 |
| Journal | Blood |
| Issue Number | 15 |
| Volume Number | 118 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2011-10-13 |
| Access Restriction | Open |
| Rights Holder | American Society of Hematology |
| Subject Keyword | Immunology Cell Biology Biochemistry Hematology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Hematology Biochemistry Immunology |
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