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BIRC6 (APOLLON) is down-regulated in acute myeloid leukemia and its knockdown attenuates neutrophil differentiation

Anna M Schläfli1, Bruce E Torbett2, Martin F Fey13 and Mario P Tschan13*

Author Affiliations

1 Experimental Oncology/Hematology, Department of Clinical Research, University of Bern, Murtenstrasse 35, CH-3010, Bern, Switzerland

2 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA

3 Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland

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Experimental Hematology & Oncology 2012, 1:25  doi:10.1186/2162-3619-1-25

Published: 4 September 2012

Abstract

Background

Inhibitors of apoptosis (IAPs) were intensively investigated in the context of cancer where they promote tumor growth and chemoresistence. Overexpression of the IAP BIRC6 is associated with unfavorable clinical features and negatively impacts relapse-free survival in childhood acute myeloid leukemia (AML). Currently, BIRC6 levels in adult primary AML have not been compared to the expression in normal myeloid cells. Thus, we compared for the first time BIRC6 levels in adult primary AML patient samples to normal myeloid cells and studied its regulation and function during neutrophil differentiation.

Findings

We found significantly lower BIRC6 levels in particular AML subtypes as compared to granulocytes from healthy donors. The lowest BIRC6 expression was found in CD34+ progenitor cells. Moreover, BIRC6 expression significantly increased during neutrophil differentiation of AML cell lines and knocking down BIRC6 in NB4 acute promyelocytic leukemia (APL) cells significantly impaired neutrophil differentiation, but not cell viability.

Conclusion

Together, we found an association of low BIRC6 levels with an immature myeloid phenotype and describe a function for BIRC6 in neutrophil differentiation of APL cells.

Keywords:
BIRC6; Acute myeloid leukemia; Acute promyelocytic leukemia; ATRA; Neutrophil differentiation