title: 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.
authors.affiliation: a Department of Bone Marrow Transplantation , West German Cancer Center , Essen , Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Koldehoff
authors.affiliation: b Institute for Transfusion Medicine , Essen , Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Lindemann
authors.affiliation: c Department of Hematology , West German Cancer Center , Essen , Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Opalka
authors.affiliation: d Department of Medical Oncology , West German Cancer Center , Essen , Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.affiliation: e Institute of Virology, University Hospital of Essen , Essen , Germany.
authors.forename: Rudolf Stefan
authors.initials: RS
authors.lastname: Ross
authors.affiliation: a Department of Bone Marrow Transplantation , West German Cancer Center , Essen , Germany.|f Department of Oncology and Hematology , HELIOS Schwerin , Schwerin , Germany.
authors.forename: Ahmet H
authors.initials: AH
authors.lastname: Elmaagacli
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D003587:Cytomegalovirus / Q000502:physiology*; D020868:Gene Silencing; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000821:virology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D007938:Leukemia; D034741:RNA, Small Interfering / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics; D014775:Virus Activation
chemical_list: D051017:Apoptosis Regulatory Proteins; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D034741:RNA, Small Interfering; D051217:Toll-Like Receptor 9; D020169:Caspases
keywords: Acute leukemia; HCMV; transplant