High incidence, early onset of histiocytic sarcomas in mice with Hertwig's anemia.
Document Type
Article
Publication Date
2005
Keywords
Crosses-Genetic, Disease-Models-Animal, Hematopoiesis-Extramedullary, Histiocytosis-Malignant, Homozygote, Incidence, Mice-Mutant-Strains, Myelopoiesis, Sarcoma
First Page
1118
Last Page
1129
JAX Source
Exp Hematol 2005 Oct; 33(10):1118-29.
Abstract
OBJECTIVE: Histiocytic sarcoma (HS) is a rare, rapidly disseminated, usually lethal tumor in humans. Treatment specific for HS has not been developed primarily due to deficiencies of appropriate animal models with high incidence/early onset. Mice with Hertwig's anemia (an/an) provide a potential model. METHODS: Here, we compare HS susceptibility in an/an and unaffected control mice maintained on three genetic backgrounds. As a potential therapeutic measure, genetically marked bone marrow is transplanted between high and low susceptibility animals. RESULTS: HS is detected earlier and the overall incidence is 15-fold higher in WBB6F1(F1)-an/an than in F1-+/?, B6-an/an and -+/? mice. Neither WB-an/an nor their normal WB-+/? littermates present with HS. Liver myelopoiesis and aneuploidy coexist with HS but the former is also rampant (33.7% incidence) in HS-free +/? and an/an mice. Marrow transplantation experiments provide evidence that (1) myelopoiesis is associated with HS and (2) early-onset/high-incidence HS is blocked by using late-onset F1-+/+ mice, as either donor or recipient. CONCLUSIONS: Homozygosity for an on an F1 genetic background is essential for high-incidence/early-onset HS; myelopoiesis and HS coexist; and therapeutic transplantation may be feasible.
Recommended Citation
Barker JE,
Deveau SA,
Compton ST,
Fancher K,
Eppig JT.
High incidence, early onset of histiocytic sarcomas in mice with Hertwig's anemia. Exp Hematol 2005 Oct; 33(10):1118-29.