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 Pelus

Research output: Contribution to journalArticle

17 Citations (Scopus)

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
Article number946936
JournalJournal of Oncology
DOIs
StatePublished - 2011

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Leukemia
Stem Cells
Genes
Hematopoietic Stem Cells
Acute Myeloid Leukemia
Cell- and Tissue-Based Therapy
Epidermal Growth Factor Receptor
Apoptosis
Mutation

ASJC Scopus subject areas

  • Oncology

Cite this

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

Survivin selectively modulates genes deregulated in human leukemia stem cells. / Fukuda, Seiji; Abe, Mariko; Onishi, Chie; Taketani, Takeshi; Purevsuren, Jamiyan; Yamaguchi, Seiji; Conway, Edward M.; Pelus, Louis.

In: Journal of Oncology, 2011.

Research output: Contribution to journalArticle

Fukuda, S, Abe, M, Onishi, C, Taketani, T, Purevsuren, J, Yamaguchi, S, Conway, EM & Pelus, L 2011, 'Survivin selectively modulates genes deregulated in human leukemia stem cells', Journal of Oncology. https://doi.org/10.1155/2011/946936
Fukuda S, Abe M, Onishi C, Taketani T, Purevsuren J, Yamaguchi S et al. Survivin selectively modulates genes deregulated in human leukemia stem cells. Journal of Oncology. 2011. 946936. https://doi.org/10.1155/2011/946936
Fukuda, Seiji ; Abe, Mariko ; Onishi, Chie ; Taketani, Takeshi ; Purevsuren, Jamiyan ; Yamaguchi, Seiji ; Conway, Edward M. ; Pelus, Louis. / Survivin selectively modulates genes deregulated in human leukemia stem cells. In: Journal of Oncology. 2011.
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AU - Yamaguchi, Seiji

AU - Conway, Edward M.

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AB - 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.

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