High incidence, early onset of histiocytic sarcomas in mice with Hertwig's anemia.
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.
Barker
Jane E
JE
The Jackson Laboratory, Bar Harbor, ME 04609, USA. jeb@jax.org
Deveau
Susan A
SA
Compton
Sheila T
ST
Fancher
Karen
K
Eppig
Janan T
JT
D000818:Animals; D016026:Bone Marrow Transplantation; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D006411:Hematopoiesis, Extramedullary / Q000235:genetics; D054747:Histiocytic Sarcoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006720:Homozygote; D006801:Humans; D015994:Incidence; D051379:Mice; D008817:Mice, Mutant Strains; D038042:Myelopoiesis / Q000235:genetics; D012509:Sarcoma / Q000235:genetics / Q000473:pathology / Q000628:therapy