Cytomegalovirus induces apoptosis in acute leukemia cells as a virus-versus-leukemia function

Abstract

Cytomegalovirus (HCMV) reactivation occurs frequently after hematopoietic stem cell transplantation and is associated with an increased treatment-related mortality. Induction of apoptosis by HCMV is unusual because HCMV utilizes various strategies to prevent apoptosis in infected cells in order to delay cell death and maintain viral replication. Here we show that HCMV can infect the acute leukemia cell lines Kasumi-1 (AML) and SD-1 (BCR-ABL-positive ALL), which inhibited their proliferation and induced apoptosis in almost all cells after 14 days. Although HCMV induced a significant up-regulation of the anti-apoptotic gene cFLIP and the anti-stress gene Gadd45a, and simultaneously down-regulated the pro-apoptotic genes p53, Gadd45gamma in Kasumi-1 and SD-1 cells, we found that these anti-apoptotic mechanisms failed in HCMV-infected acute leukemia cells and apoptosis occurred via a caspase-dependent pathway. We conclude that HCMV can provide anti-leukemic effects in vitro. To determine if this phenomenon may be clinically relevant further investigations will be required.

Keywords::

• Acute leukemia
• HCMV
• transplant

Acknowledgements

The authors would like to thank Silke Maag, Roberta Freese, Stefanie Lorenzen, Melanie Lang, Sandra Christoph, Thomas Mühlenberg, Martina Franke, Ines Riepenhoff, Liana Baatsch, Karin Krause, Maria Hüttemann (all Essen, Germany) for their excellent technical assistance.

Potential conflict of interest:

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This work was supported by grants from the Kulturstiftung Essen.