Expression, adverse prognostic significance and therapeutic small molecule inhibition of Polo-like kinase 1 in multiple myeloma

被引：16

作者：

Evans, Robert P. ^{[1
]}

Dueck, Greg ^{[1
]}

Sidhu, Roger ^{[1
]}

Ghosh, Sunita ^{[1
]}

Toman, Inka ^{[1
]}

Loree, Jonathan ^{[1
]}

Bahlis, Nizar ^{[1
]}

Klimowicz, Alexander C. ^{[1
]}

Fung, Joyce ^{[1
]}

Jung, Michelle ^{[1
]}

Lai, Raymond ^{[1
]}

Pilarski, Linda M. ^{[1
]}

Belch, Andrew R. ^{[1
]}

Reiman, Tony ^{[1
]}

机构：

[1] St Johns Hosp, Dept Oncol, St John, NB E2L 4L2, Canada

来源：

LEUKEMIA RESEARCH | 2011年 / 35卷 / 12期

关键词：

Polo-like kinase 1; PLK1; Multiple myeloma; Novel therapeutics; RISK STRATIFICATION; DIAGNOSIS; CELLS; PLK;

D O I：

10.1016/j.leukres.2011.07.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The amplified myeloma centrosome has been identified as a therapeutic target. The present study explored the expression and prognostic significance of the centrosome-associated protein PLK1 in myeloma and the effect of BI 2536, a potent and selective inhibitor of PLK1, on myeloma cells. High plasma cell expression of PLK1 protein in myeloma patient bone marrow biopsies is an independent adverse prognostic factor (HR = 2.3, p = 0.003 unadjusted; HR = 1.9, p = 0.03 in multivariable model). BI 2536 inhibits myeloma cell lines at nanomolar concentrations, and is therapeutic for xenografts in NOD/SCID mice. PLK1 inhibition is a potential new strategy for the treatment of multiple myeloma. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1637 / 1643

页数：7

共 27 条

[1] Automated subcellular localization and quantification of protein expression in tissue microarrays [J].

Camp, RL ;

Chung, GG ;

Rimm, DL .

NATURE MEDICINE, 2002, 8 (11) :1323-1327

[2] Risk stratification of patients with newly diagnosed multiple myeloma: Optimizing treatment based on pretreatment characteristics [J].

Chng, Wee J. ;

Fonseca, Rafael .

CLINICAL LYMPHOMA & MYELOMA, 2005, 6 (03) :200-207

[3] Clinical implication of centrosome amplification in plasma cell neoplasm [J].

Chng, WJ ;

Ahmann, GJ ;

Henderson, K ;

Santana-Davila, R ;

Greipp, PR ;

Gertz, MA ;

Lacy, MQ ;

Dispenzieri, A ;

Kumar, S ;

Rajkumar, SV ;

Lust, JA ;

Kyle, RA ;

Zeldenrust, SR ;

Hayman, SR ;

Fonseca, R .

BLOOD, 2006, 107 (09) :3669-3675

[4] IDENTIFICATION AND CLONING OF A PROTEIN KINASE-ENCODING MOUSE GENE, PLK, RELATED TO THE POLO GENE OF DROSOPHILA [J].

CLAY, FJ ;

MCEWEN, SJ ;

BERTONCELLO, I ;

WILKS, AF ;

DUNN, AR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (11) :4882-4886

[5] Polo-like kinases and oncogenesis [J].

Eckerdt, F ;

Yuan, JP ;

Strebhardt, K .

ONCOGENE, 2005, 24 (02) :267-276

[6] Consensus statement from European experts on the diagnosis, management, and treatment of multiple myeloma: from standard therapy to novel approaches [J].

Engelhardt, Monika ;

Kleber, Martina ;

Udi, Josefina ;

Waesch, Ralph ;

Spencer, Andrew ;

Patriarca, Francesca ;

Knop, Stefan ;

Bruno, Benedetto ;

Gramatzki, Martin ;

Morabito, Fortunato ;

Kropff, Martin ;

Neri, Antonin ;

Sezer, Orhan ;

Hajek, Rom ;

Bunjes, Donald ;

Boccadoro, Mario ;

Straka, Christian ;

Cavo, Michele ;

Polliack, Aaron ;

Einsele, Hermann ;

Palumbo, Antonio .

LEUKEMIA & LYMPHOMA, 2010, 51 (08) :1424-1443

[7] Aurora A kinase RNAi and small molecule inhibition of Aurora kinases with VE-465 induce apoptotic death in multiple myeloma cells [J].

Evans, Robert ;

Naber, Claudia ;

Steffler, Tara ;

Checkland, Tamara ;

Keats, Jonathan ;

Maxwell, Christopher ;

Perry, Troy ;

Chau, Heidi ;

Belch, Andrew ;

Pilarski, Linda ;

Reiman, Tony .

LEUKEMIA & LYMPHOMA, 2008, 49 (03) :559-569

[8] The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma [J].

Evans, Robert P. ;

Naber, Claudia ;

Steffler, Tara Summary ;

Checkland, Tamara ;

Maxwell, Christopher A. ;

Keats, Jonathan J. ;

Belch, Andrew R. ;

Pilarski, Linda M. ;

Lai, Raymond ;

Reiman, Tony .

BRITISH JOURNAL OF HAEMATOLOGY, 2008, 140 (03) :295-302

[9] A CONSERVED MITOTIC KINASE ACTIVE AT LATE ANAPHASE TELOPHASE IN SYNCYTIAL DROSOPHILA EMBRYOS [J].

FENTON, B ;

GLOVER, DM .

NATURE, 1993, 363 (6430) :637-640

[10] Polo-like kinases: a team that plays throughout mitosis [J].

Glover, DM ;

Hagan, IM ;

Tavares, AAM .

GENES & DEVELOPMENT, 1998, 12 (24) :3777-3787

← 1 2 3 →