High incidence, early onset of histiocytic sarcomas in mice with Hertwig's anemia

Exp Hematol. 2005 Oct;33(10):1118-29. doi: 10.1016/j.exphem.2005.06.021.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Transplantation
  • Crosses, Genetic*
  • Disease Models, Animal*
  • Hematopoiesis, Extramedullary / genetics
  • Histiocytic Sarcoma* / genetics
  • Histiocytic Sarcoma* / pathology
  • Histiocytic Sarcoma* / therapy
  • Homozygote
  • Humans
  • Incidence
  • Mice
  • Mice, Mutant Strains
  • Myelopoiesis / genetics
  • Sarcoma* / genetics
  • Sarcoma* / pathology
  • Sarcoma* / therapy