Efficacy of the polo-like kinase inhibitor rigosertib, alone or in combination with abelson tyrosine kinase inhibitors, against break point cluster region-c-Abelson-positive leukemia cells

Seiichi Okabe; Tetsuzo Tauchi; Yuko Tanaka; Juri Sakuta; Kazuma Ohyashiki

doi:10.18632/oncotarget.4047

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

Efficacy of the polo-like kinase inhibitor rigosertib, alone or in combination with abelson tyrosine kinase inhibitors, against break point cluster region-c-Abelson-positive leukemia cells

Seiichi Okabe _, Tetsuzo Tauchi, Yuko Tanaka, Juri Sakuta and Kazuma Ohyashiki

PDF | HTML | How to cite

Oncotarget. 2015; 6:20231-20240. https://doi.org/10.18632/oncotarget.4047

Metrics: PDF 1818 views | HTML 2270 views | ?

Abstract

Seiichi Okabe1, Tetsuzo Tauchi1, Yuko Tanaka1, Juri Sakuta1 and Kazuma Ohyashiki1

1 Department of Hematology, Tokyo Medical University, Tokyo, Japan

Correspondence to:

Seiichi Okabe, email:

Keywords: chronic myeloid leukemia, ABL tyrosine kinase inhibitor, resistant cell, polo-like kinase

Received: January 21, 2015 Accepted: April 22, 2015 Published: May 08, 2015

Abstract

The potency of Abelson (ABL) tyrosine kinase inhibitors (TKIs) against chronic myeloid leukemia (CML) has been demonstrated. However, ABL TKI resistance can develop. In this study, we investigated the efficacy of a combination therapy including rigosertib (ON 01910.Na), a polo-like kinase (PLK) and phosphoinositide 3-kinase (PI3K) inhibitor, and ABL TKIs. A 72-h rigosertib treatment was found to inhibit cell growth, induce apoptosis, reduce phosphorylation of the breakpoint cluster region-c (BCR)-ABL and its substrate Crk-L, and increase the activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). This combination therapy also exerted a synergistic inhibitory effect on Philadelphia chromosome (Ph)-positive cell proliferation and reduced the phosphorylation of BCR-ABL and Crk-L while increasing that of cleaved PARP and the H2A.X histone. Rigosertib also potently inhibited the growth of ABL TKI-resistant cells, and cotreatment with ABL TKIs and rigosertib induced higher cytotoxicity. These results indicate that rigosertib treatment may be a powerful strategy against ABL TKI-resistant cells and could enhance the cytotoxic effects of ABL TKIs.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 4047

Publication Alerts

Research Papers:

Efficacy of the polo-like kinase inhibitor rigosertib, alone or in combination with abelson tyrosine kinase inhibitors, against break point cluster region-c-Abelson-positive leukemia cells

Abstract