A novel treatment strategy targeting shugoshin 1 in hematological malignancies

Shugoshin 1 (SGOL1), a centromeric protein, plays an important role in mitosis. This study explored the levels of SGOL1 in hematological malignancies and found that SGOL1 was aberrantly expressed in various 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 realtime 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 small interfering RNA (siRNA) slowed the proliferation of NB4, EOL-1 and U937 cells compared with the control siRNA transfected cells, in parallel with the appearance of precocious dissociation of centromeric cohesion and separation of sister chromatids in these cells. Furthermore, we found that repression of SGOL1 by siRNA accumulated EOL-1 and U937 cells in the G2/M phase of the cell cycle, in conjunction with up-regulation of the spindle checkpoint protein BubR1, followed by apoptosis via caspase pathways. Thus, SGOL1 might be a promising molecular target for treating individuals with AML. (C) 2012 Elsevier Ltd. All rights reserved.