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

Robert P Evans; Greg Dueck; Roger Sidhu; Sunita Ghosh; Inka Toman; Jonathan Loree; Nizar Bahlis; Alexander C Klimowicz; Joyce Fung; Michelle Jung; Raymond Lai; Linda M Pilarski; Andrew R Belch; Tony Reiman

doi:10.1016/j.leukres.2011.07.016

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

Leuk Res. 2011 Dec;35(12):1637-43. doi: 10.1016/j.leukres.2011.07.016. Epub 2011 Aug 3.

Authors

Robert P Evans¹, Greg Dueck, Roger Sidhu, Sunita Ghosh, Inka Toman, Jonathan Loree, Nizar Bahlis, Alexander C Klimowicz, Joyce Fung, Michelle Jung, Raymond Lai, Linda M Pilarski, Andrew R Belch, Tony Reiman

Affiliation

¹ Department of Oncology; Saint John Regional Hospital, Saint John, NB, Canada.

PMID: 21816470
DOI: 10.1016/j.leukres.2011.07.016

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Biomarkers, Tumor / genetics
Cell Cycle Proteins / antagonists & inhibitors*
Cell Cycle Proteins / genetics*
Cell Cycle Proteins / metabolism
Drug Resistance, Neoplasm / genetics
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
Male
Mice
Mice, Inbred NOD
Mice, SCID
Middle Aged
Multiple Myeloma / diagnosis*
Multiple Myeloma / drug therapy*
Multiple Myeloma / genetics*
Polo-Like Kinase 1
Prognosis
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use*
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Protein Serine-Threonine Kinases / genetics*
Protein Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / antagonists & inhibitors*
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins / metabolism
Retrospective Studies
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology
Treatment Outcome
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents
Biomarkers, Tumor
Cell Cycle Proteins
Protein Kinase Inhibitors
Proto-Oncogene Proteins
Small Molecule Libraries
Protein Serine-Threonine Kinases