SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target

被引：103

作者：

Christensen, Dale J. ^{[1
,2
]}

Chen, Youwei ^{[2
]}

Oddo, Jessica ^{[1
]}

Matta, Karen M. ^{[2
]}

Neil, Jessica ^{[1
]}

Davis, Evan D. ^{[2
]}

Volkheimer, Alicia D. ^{[3
]}

Lanasa, Mark C. ^{[2
]}

Friedman, Daphne R. ^{[2
]}

Goodman, Barbara K. ^{[2
]}

Gockerman, Jon P. ^{[2
]}

Diehl, Louis F. ^{[2
]}

de Castro, Carlos M. ^{[2
]}

Moore, Joseph O. ^{[2
]}

Vitek, Michael P. ^{[1
,2
]}

Weinberg, J. Brice ^{[2
,3
]}

机构：

[1] Oncotide Pharmaceut, Durham, NC USA

[2] Duke Univ, Med Ctr, Durham, NC USA

[3] Durham Vet Adm Med Ctr, Durham, NC USA

来源：

BLOOD | 2011年 / 118卷 / 15期

关键词：

PROTEIN PHOSPHATASE 2A; NITRIC-OXIDE SYNTHASE; APOLIPOPROTEIN-E; IN-VITRO; MCL-1; EXPRESSION; TUMOR-SUPPRESSOR; P38; MAPK; APOPTOSIS; CANCER; SURVIVAL;

D O I：

10.1182/blood-2011-04-351072

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2011; 118(15):4150-4158)

引用

页码：4150 / 4158

页数：9

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