The shugoshin 1(SGOL1), a member of centromeric proteins, plays an important role in mitosis. The present study explored the levels of SGOL1 in hematological malignancies and found that SGOL1 was aberrantly expressed in various types of human leukemia cell lines (n=10, e.g., HL60, U937, MOLM-13, K562, EOL-1, etc.) and freshly isolated leukemia cells from individuals with acute myelogenous leukemia (AML, n=43, p<0.001) compared with bone marrow mononuclear cells isolated from healthy volunteers (n=9), as measured by real-time RT-PCR. Forced-expression of SGOL1 in hematopoietic stem/progenitor cells (HSPCs) significantly increased colony numbers for CFU-M and CFU-GM compared with control vector transduced infected HSPCs, suggesting that SGOL1 might act as an oncogene in hematopoietic cells. In addition, we found that repression of SGOL1 by a small interfering RNA (siRNA) slowed the proliferation of NB4, EOL-1 and U937 cells compared to the control siRNA transfected cells, in parallel with appearance of precocious dissociation of centromeric cohesion and separation of sister chromatids in these cells. Furthermore, we found that repression of SGOL1 by an siRNA accumulated EOL-1 and U937 cells in the G2/M phase of the cell cycle, in conjunction with up-regulation of spindle checkpoint protein BubR1, followed by apoptosis via caspase pathways. Taken together, SGOL1 may be a promising molecular target for individuals with AML.

Citation Format: Takayuki Ikezoe, Jing Yang, Chie Nishioka, Akihito Yokoyama. A novel treatment strategy targeting shugoshin 1 in hematological malignancies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5599. doi:10.1158/1538-7445.AM2013-5599

Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

©2013 American Association for Cancer Research
2013