Survivin is highly expressed in CD34 +38 - leukemic stem/progenitor cells and predicts poor clinical outcomes in AML

Bing Z. Carter, Yihua Qiu, Xuelin Huang, Lixia Diao, Nianxiang Zhang, Kevin R. Coombes, Duncan H. Mak, Marina Konopleva, Jorge Cortes, Hagop M. Kantarjian, Gordon B. Mills, Michael Andreeff, Steven M. Kornblau

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Survivin, a member of the inhibitors of apoptosis protein family, plays important roles in cell proliferation and survival and is highly expressed in various malignancies, including leukemias. To better understand its role in acute myeloid leukemia (AML), we profiled survivin expression in samples obtained from 511 newly diagnosed AML patients and in CD34 +38 - AML stem/progenitor cells using a validated reverse-phase protein array; we correlated its levels with clinical outcomes and with levels of other proteins in the same sample set. We found that survivin levels were higher in bone marrow than in paired peripheral blood leukemic cells (n = 140, P = .0001) and that higher survivin levels significantly predicted shorter overall (P = .016) and event-free (P = .023) survival in multivariate Cox model analysis. Importantly, survivin levels were significantly higher in CD34 +38 - AML stem/progenitor cells than in bulk blasts and total CD34 + AML cells (P < .05). Survivin expression correlated with the expressions of multiple proteins involved with cell proliferation and survival. Particularly, its expression strongly correlated with HIF1α in the stem/progenitor cell compartment. These results suggest that survivin is a prognostic biomarker in AML and that survivin, which is overexpressed in AML stem/progenitor cells, remains a potentially important target for leukemia therapy.

Original languageEnglish (US)
Pages (from-to)173-180
Number of pages8
JournalBlood
Volume120
Issue number1
DOIs
Publication statusPublished - Jul 5 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Carter, B. Z., Qiu, Y., Huang, X., Diao, L., Zhang, N., Coombes, K. R., ... Kornblau, S. M. (2012). Survivin is highly expressed in CD34 +38 - leukemic stem/progenitor cells and predicts poor clinical outcomes in AML. Blood, 120(1), 173-180. https://doi.org/10.1182/blood-2012-02-409888