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Journal of Oncology
Volume 2011, Article ID 946936, 14 pages
Research Article

Survivin Selectively Modulates Genes Deregulated in Human Leukemia Stem Cells

1Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya-Cho, Izumo, Shimane 693-8501, Japan
2Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202-5254, USA
3Department of Hematology, Shimane University School of Medicine, Shimane 693-8501, Japan
4Division of Blood Transfusion, Shimane University Hospital, Shimane 693-8501, Japan
5Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada V6T 1Z3

Received 1 September 2010; Accepted 19 October 2010

Academic Editor: Shih Hwa Chiou

Copyright © 2011 Seiji Fukuda et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


ITD-Flt3 mutations are detected in leukemia stem cells (LSCs) in acute myeloid leukemia (AML) patients. While antagonizing Survivin normalizes ITD-Flt3-induced acute leukemia, it also impairs hematopoietic stem cell (HSC) function, indicating that identification of differences in signaling pathways downstream of Survivin between LSC and HSC are crucial to develop selective Survivin-based therapeutic strategies for AML. Using a Survivin-deletion model, we identified 1,096 genes regulated by Survivin in ITD-Flt3-transformed c-kit+, Sca-1+, and lineageneg (KSL) cells, of which 137 are deregulated in human LSC. Of the 137, 124 genes were regulated by Survivin exclusively in ITD-Flt3+ KSL cells but not in normal CD34neg KSL cells. Survivin-regulated genes in LSC connect through a network associated with the epidermal growth factor receptor signaling pathway and falls into various functional categories independent of effects on apoptosis. Pathways downstream of Survivin in LSC that are distinct from HSC can be potentially targeted for selective anti-LSC therapy.