title: Murine retroviral bone marrow transplantation models for the study of human myeloproliferative disorders.
abstract: Human myeloproliferative diseases are common hematologic disorders characterized by clonal overproduction of maturing myeloid or erythroid cells, often caused by expression of a mutant, dysregulated tyrosine kinase (TK). These diseases can be accurately modeled in laboratory mice by the retroviral transfer of a mutant TK gene into murine hematopoietic stem and progenitor cells, followed by transplantation of these cells into irradiated recipient mice. This yields a model system for analyzing the molecular pathophysiology of these conditions and provides a platform for testing therapies, particularly molecularly targeted new chemical entities (NCEs). The Basic Protocol in this unit describes the preparation of mouse bone marrow cells to express the relevant human oncogene before transplanting them into irradiated recipient mice. An alternate protocol describes a similar technique that allows specific induction of lymphoproliferative disease by some TKs. Support protocols for generating and titering retroviral stocks are also included.
authors.affiliation: Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: L Cristina
authors.initials: LC
authors.lastname: Gavrilescu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Van Etten
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000379:methods*; D003470:Culture Media / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D016313:Genes, abl / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000235:genetics*; D009368:Neoplasm Transplantation / Q000379:methods; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012190:Retroviridae; D013048:Specimen Handling / Q000379:methods; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D003470:Culture Media; D016207:Cytokines; D011505:Protein-Tyrosine Kinases; D005472:Fluorouracil