title: Differential expression and function of CD27 in chronic lymphocytic leukemia cells expressing ZAP-70.
abstract: Chronic lymphocytic leukemia is a malignancy driven by abberant B cell signaling and survival. Leukemic B cells accumulate in the peripheral blood and the lymphoid organs where contact with stromal cells and T cells provide critical survival signals. Clinical severity of CLL is associated with several prognostic markers including expression of the kinase ZAP-70. ZAP-70 expression enhances signaling via the B cell antigen receptor and is associated with increased cell adhesion and migration capacity. Here we report that ZAP-70-positive CLL patients display significantly higher expression of the TNF superfamily receptor and memory marker CD27 than do ZAP-70 negative patients. CD27 expression by CLL was acutely elevated upon BCR cross-linking, or upon ectopic expression of ZAP-70. CD27 expression correlated with functional capacity to adhere to stromal cells and antibody blockade of CD27 impaired CLL binding to stroma. These results provide the first evidence for differential expression of CD27 among CLL prognostic groups, suggest a role for ZAP-70 dependent signaling in CD27 induction and implicate CD27 in cell-cell interactions with the lymphoid tissue microenvironment.
authors.affiliation: University of Manitoba, Department of Immunology, Winnipeg, MB, Canada; CancerCare Manitoba, Manitoba Institute of Cell Biology, Winnipeg, MB, Canada.
authors.forename: Sandrine T
authors.initials: ST
authors.lastname: Lafarge
authors.affiliation: University of Manitoba, Department of Immunology, Winnipeg, MB, Canada.
authors.forename: Sen
authors.initials: S
authors.lastname: Hou
authors.affiliation: University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB, Canada.
authors.forename: Samantha D
authors.initials: SD
authors.lastname: Pauls
authors.affiliation: CancerCare Manitoba, Manitoba Institute of Cell Biology, Winnipeg, MB, Canada.
authors.forename: James B
authors.initials: JB
authors.lastname: Johnston
authors.affiliation: University of Manitoba, Department of Immunology, Winnipeg, MB, Canada; CancerCare Manitoba, Manitoba Institute of Cell Biology, Winnipeg, MB, Canada; University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB, Canada.
authors.forename: Spencer B
authors.initials: SB
authors.lastname: Gibson
authors.affiliation: University of Manitoba, Department of Immunology, Winnipeg, MB, Canada; University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB, Canada. Electronic address: aaron.marshall@med.umanitoba.ca.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Marshall
mesh_terms: D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism*
chemical_list: D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D051746:ZAP-70 Protein-Tyrosine Kinase
keywords: Adhesion; CD27; Chronic lymphocytic leukemia; ZAP-70