title: Megakaryocyte growth and development factor ameliorates carboplatin-induced thrombocytopenia in mice.
abstract: Megakaryocyte growth and development factor (MGDF) administered intraperitoneally (IP) to mice causes a dose-dependent thrombocytosis accompanied by a decrease in mean platelet volume. MGDF increases the number of megakaryocytes in the bone marrow and spleen. MGDF does not affect the circulating number of leukocytes. Carboplatin, a chemotherapeutic agent that causes thrombocytopenia in humans, administered to mice as a single IP injection at a nonlethal dose causes a significant, but reversible thrombocytopenia. The carboplatin-induced thrombocytopenia is accompanied by an increase in circulating endogenous MGDF that precedes the return of circulating platelets to a normal level. MGDF mRNA is constitutively present in the liver. After carboplatin treatment, hepatic MGDF mRNA does not increase in concordance with circulating MGDF. Circulating soluble MGDF receptor levels (c-mpl) do not change significantly during the course of carboplatin-induced thrombocytopenia. MGDF injected IP once daily beginning 1 day after injection of carboplatin reverses carboplatin-induced thrombocytopenia in a dose-dependent fashion. The normalization of circulating platelet numbers in carboplatin plus MGDF-treated mice is accompanied by a normalization of megakaryocyte numbers in the bone marrow. In conclusion, MGDF, by increasing the number of marrow megakaryocytes and circulating platelets is an effective therapy for carboplatin-induced thrombocytopenia in mice.
authors.affiliation: Amgen Inc., Thousand Oaks, CA 91320, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Ulich
authors.forename: J
authors.initials: J
authors.lastname: del Castillo
authors.forename: S
authors.initials: S
authors.lastname: Yin
authors.forename: S
authors.initials: S
authors.lastname: Swift
authors.forename: D
authors.initials: D
authors.lastname: Padilla
authors.forename: G
authors.initials: G
authors.lastname: Senaldi
authors.forename: L
authors.initials: L
authors.lastname: Bennett
authors.forename: J
authors.initials: J
authors.lastname: Shutter
authors.forename: J
authors.initials: J
authors.lastname: Bogenberger
authors.forename: D
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D016190:Carboplatin / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006410:Hematopoiesis / Q000187:drug effects; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins; D013921:Thrombocytopenia / Q000188:drug therapy*; D013926:Thrombopoietin / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D013926:Thrombopoietin; D016190:Carboplatin