title: Gemtuzumab ozogamicin (Mylotarg) upregulates tissue factor expression but not secretion of inflammatory cytokines TNF-alpha or IL-8.
abstract: Gemtuzumab ozogamicin (GO; Mylotarg (R)) is an antibody-targeted chemotherapeutic agent approved for the treatment of CD33+ acute myelogenous leukemia (AML). GO is more commonly associated with the development of Sinusoidal Obstructive Syndrome (SOS) than any other chemotherapeutic agent in this patient group. Previous investigations have shown that SOS is a pro-coagulant and pro-inflammatory syndrome. Treatment of THP1 cells (CD33+ AML cell line) with GO alone, or in combination with unconjugated CD33 antibody (hP67.6), resulted in a statistically significant (P<0.01) increase in tissue factor (TF) expression, but HepG2 cells (CD33 hepatocyte cell line) were unaffected. Cytokine secretion was not affected by GO treatment in either cell line. These results indicate that GO exerts a pro-coagulant response in certain cell types, which may predispose individuals to developing SOS.
authors.affiliation: Department of Haematology, Trinity College, Dublin, Ireland.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bruneau
authors.forename: Aengus
authors.initials: A
authors.lastname: O'Marcaigh
authors.forename: Owen P
authors.initials: OP
authors.lastname: Smith
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D000079982:Gemtuzumab; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin; D000079982:Gemtuzumab