title: Retrovirus-transformed erythroleukemia cells induce central nervous system failure in a new syngeneic mouse model of meningeal leukemia.
abstract: Lack of suitable mouse models for central nervous system (CNS)-associated leukemias has hindered mechanism-guided development of therapeutics. By transplanting retrovirus-transformed mouse erythroleukemia cells into syngeneic mice, we developed a new animal model of meningeal leukemia associated with rapid paralysis. Necropsy revealed massive proliferation of the leukemic cells in the bone marrow (BM) followed by pathological angiogenesis and invasion of the leukemic cells into the meninges of the CNS. Further analysis demonstrated that the erythroleukemia cells secreted high levels of VEGF and preferentially adhered in vitro to fibronectin. This unique animal model for meningeal leukemia should facilitate studies of engraftment and proliferation of leukemic cells in the BM and their invasion of the CNS as well as pre-clinical evaluation of experimental therapeutics for CNS-associated leukemias.
authors.affiliation: Laboratory of Cancer Prevention, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA.
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Macpherson
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Hanson
authors.forename: Delores M
authors.initials: DM
authors.lastname: Thompson
authors.forename: Christine M
authors.initials: CM
authors.lastname: Perella
authors.forename: Joan L
authors.initials: JL
authors.lastname: Cmarik
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Ruscetti
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D049109:Cell Proliferation; D016543:Central Nervous System Neoplasms / Q000098:blood supply / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism; D020869:Gene Expression Profiling; D039081:Integrin alpha5beta1 / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000503:physiopathology*; D007942:Leukemia, Experimental / Q000209:etiology / Q000473:pathology*; D008577:Meningeal Neoplasms / Q000098:blood supply / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D012190:Retroviridae / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005353:Fibronectins; D039081:Integrin alpha5beta1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse