1. ¹Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Kochi, Japan
2. ²Department of Surgery, Kochi University, Nankoku, Kochi, Japan
3. ³Department of Laboratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan
4. ⁴Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA

Correspondence: Dr T Ikezoe, Department of Hematology and Respiratory Medicine, Kochi University, Okoh-cho, Nankoku, Kochi 783-8505, Japan. E-mail: ikezoet@kochi-u.ac.jp

Received 8 November 2008; Revised 31 March 2009; Accepted 1 April 2009; Published online 7 May 2009.

Abstract

Objectives: Polo-like kinase1 (PLK1) belongs to the family of serine/threonine kinases and plays an important role in centrosome maturation, bipolar spindle formation, and cytokinesis during mitosis. We found in this study that PLK1 was aberrantly highly expressed in a variety of human leukemia cell lines (n=20), as well as, freshly isolated leukemia cells from individuals with acute myelogenous leukemia (n=50) and acute lymphoblastic leukemia (n=15) compared with bone marrow mononuclear cells from healthy volunteers (n=13) (acute myelogenous leukemia, P=0.016; acute lymphoblastic leukemia, P=0.008), as measured by real-time RT–PCR. Downregulation of PLK1 by a small interfering RNA in NB4 acute myelogenous leukemia cells inhibited their proliferation. GW843682X is a novel selective PLK1 inhibitor. The compound-induced growth inhibition, caused accumulation of cells in the G2/M phase of the cell cycle and mediated apoptosis of human leukemia cells. Pre-treatment of cells with the caspase inhibitor Z-VAD-FMK attenuated the action of GW843682X in leukemia cells, indicating the involvement of the caspase pathway in the PLK1 inhibitor-mediated apoptosis. Furthermore, we found that the PLK1 inhibitor synergistically potentiated the growth inhibition and apoptosis of leukemia cells when combined with tubulin-depolymerizing agent vincristine. Taken together, targeting PLK1 may be a promising treatment strategy for individuals with leukemia.