Survivin is Highly Expressed in CD34(+)38(-) Leukemic Stem/progenitor Cells and Predicts Poor Clinical Outcomes in AML

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2012 May 31

PMID 22645176

Citations 55

Authors

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

Affiliations

Soon will be listed here.

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.

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