title: Myeloproliferative disease in transgenic mice expressing P230 Bcr/Abl: longer disease latency, thrombocytosis, and mild leukocytosis.
abstract: P230 Bcr/Abl has been associated with indolent myeloproliferative disease (MPD). We generated transgenic mice expressing P230Bcr/Abl driven by the promoter of the long terminal repeat of the murine stem cell virus of the MSCV neo P230 BCR/ABL vector. Two founder mice exhibited mild granulocytosis and marked thrombocytosis and developed MPD. The disease of one founder mouse, no. 13, progressed to extramedullary myeloblastic crisis in the liver at 12 months old. The other founder mouse, no. 22, was found to have chronic-phase MPD with large populations of megakaryocytes and granulocytes in an enlarged spleen. The transgenic progeny of no. 22 clearly exhibited MPD at 15 months old. These results showed that P230Bcr/Abl had leukemogenic properties and induced MPD. The phenotype of the MPD caused by P230Bcr/Abl was characterized by mild granulocytosis, a high platelet count, infiltration of megakaryocytes in some organs, and a longer disease latency compared with the MPD caused by P210Bcr/Abl.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. inokuchi@nms.ac.jp
authors.forename: Koiti
authors.initials: K
authors.lastname: Inokuchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Dan
authors.forename: Miyuki
authors.initials: M
authors.lastname: Takatori
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Takahuji
authors.forename: Naoya
authors.initials: N
authors.lastname: Uchida
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Inami
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyake
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Honda
authors.forename: Hisamaru
authors.initials: H
authors.lastname: Hirai
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D005822:Genetic Vectors; D007964:Leukocytosis / Q000209:etiology; D051379:Mice; D008822:Mice, Transgenic; D009196:Myeloproliferative Disorders / Q000150:complications / Q000209:etiology / Q000473:pathology*; D010641:Phenotype; D013922:Thrombocytosis / Q000209:etiology; D019076:Transgenes
chemical_list: D016044:Fusion Proteins, bcr-abl