Cytokine-regulated expression of survivin in myeloid leukemia

Bing Z. Carter, Michele Milella, Dario C. Altieri, Michael Andreeff

Research output: Contribution to journalArticle

Abstract

Survivin, a member of the inhibitors-of-apoptosis gene family, is expressed in a cell-cycle-dependent manner in all the most common cancers but not in normal differentiated adult tissues. Survivin expression and regulation were examined in acute myeloid leukemia (AML). Survivin was detected by Western blot analysis in all myeloid leukemia cell lines and in 16 of 18 primary AML samples tested. In contrast, normal CD34+ cells and normal peripheral blood mononuclear cells expressed no or very low levels of survivin. Cytokine stimulation increased survivin expression in leukemic cell lines and in primary AML samples. In cultured primary samples, single-cytokine stimulation substantially increased survivin expression in comparison with control cells, and the combination of G-CSF, GM-CSF, and SCF increased survivin levels even further. Conversely, all-trans retinoic acid significantly decreased survivin protein levels in HL-60, OCI-AML3, and NB-4 cells within 96 hours, parallel to the induction of myelomonocytic differentiation. Using selective pharmacologic inhibitors, the differential involvement of mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol-3 kinase (PI3K) pathways were demonstrated in the regulation of survivin expression. The MEK inhibitor PD98059 down-regulated survivin expression in both resting and GM-CSF-stimulated OCI-AML3 cells, whereas the PI3K inhibitor LY294002 inhibited survivinexpression only on GM-CSF stimulation. In conclusion, these results demonstrate that survivin is highly expressed and cytokine-regulated in myeloid leukemias and suggest that hematopoietic cytokines exert their antiapoptotic and mitogenic effects, at least in part, by increasing survivin levels.

Original languageEnglish
Pages (from-to)2784-2790
Number of pages7
JournalBlood
Volume97
Issue number9
DOIs
Publication statusPublished - May 1 2001

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Myeloid Leukemia
Granulocyte-Macrophage Colony-Stimulating Factor
Mitogen-Activated Protein Kinase Kinases
Acute Myeloid Leukemia
Phosphatidylinositol 3-Kinase
Cytokines
Cells
Cell Line
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Granulocyte Colony-Stimulating Factor
Myeloid Cells
Tretinoin
Blood Cells
Cell Cycle
Blood
Genes
Western Blotting
Tissue
Apoptosis
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Cytokine-regulated expression of survivin in myeloid leukemia. / Carter, Bing Z.; Milella, Michele; Altieri, Dario C.; Andreeff, Michael.

In: Blood, Vol. 97, No. 9, 01.05.2001, p. 2784-2790.

Research output: Contribution to journalArticle

Carter, BZ, Milella, M, Altieri, DC & Andreeff, M 2001, 'Cytokine-regulated expression of survivin in myeloid leukemia', Blood, vol. 97, no. 9, pp. 2784-2790. https://doi.org/10.1182/blood.V97.9.2784
Carter, Bing Z. ; Milella, Michele ; Altieri, Dario C. ; Andreeff, Michael. / Cytokine-regulated expression of survivin in myeloid leukemia. In: Blood. 2001 ; Vol. 97, No. 9. pp. 2784-2790.
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