Survivin selectively modulates genes deregulated in human leukemia stem cells

Seiji Fukuda, Mariko Abe, Chie Onishi, Takeshi Taketani, Jamiyan Purevsuren, Seiji Yamaguchi, Edward M. Conway, Louis M. Pelus

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number946936
JournalJournal of Oncology
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Oncology

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    Fukuda, S., Abe, M., Onishi, C., Taketani, T., Purevsuren, J., Yamaguchi, S., Conway, E. M., & Pelus, L. M. (2011). Survivin selectively modulates genes deregulated in human leukemia stem cells. Journal of Oncology, [946936]. https://doi.org/10.1155/2011/946936