Chronic infection of Fv-2-resistant hemopoietic cells by friend spleen focus-forming virus Leukemogenesis and control of stem cell differentiation by Fv-2
| Autor: | Kristine L. Hettrick, Robert J. Eckneri |
|---|---|
| Rok vydání: | 1982 |
| Předmět: |
Leukemia
Experimental Cellular differentiation Friend virus Spleen Biology Hematopoietic Stem Cells medicine.disease biology.organism_classification Virology Virus Friend murine leukemia virus Mice Haematopoiesis Leukemia medicine.anatomical_structure Erythropoietin hemic and lymphatic diseases medicine Animals Leukemia Erythroblastic Acute Stem cell medicine.drug |
| Zdroj: | Virology. 122:171-185 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/0042-6822(82)90386-5 |
| Popis: | Isologous bone marrow chimeras were prepared using adult Fv-2 resistant syngeneic C57 BL/6 (B6) mice. Exposure of the Fv-2rr donor to Friend virus (FV) complex [containing defective spleen focus-forming virus (SFFV) and NB-tropic helper (LLV-F)], or to LLV alone, at the time of engraftment resulted in the chronic infection of these chimeras by both viruses and in the appearance of erythropoietin (Epo)-independent erythroid progenitor cells (i.e., BFU-E, CFU-E). This SFFV-inductive event occurred in two phases. The first was transient and occurred in all mice early after infection while BFU-E were in cycle. The second phase occurred late (∼ Day 120) and was associated with leukemia induction. Since all mice within the SFFV/LLV study replicated virus that was demonstrably leukemogenic in Fv-2ss mice, and since only 12% of the viremic Fv-2rr B6 → B6 chimeras developed a malignant erythroleukemia with splenomegaly and polycythemia, we conclude that Fv-2 control of the proliferative state of erythroid progenitors is separable from Fv-2 control of leukemia induction by SFFV. Further, while SFFV+ B6 cells uneventfully repopulated B6 secondary recipients, congenic B6.C (Fv-2ss) recipients became ill 20–40 days after engraftment due to the outgrowth of a leukemia of donor origin. These results show that SFFV+ B6 donors contained preleukemic or “dormant” tumor. Interaction of these SFFV+ stem cells with the Fv-2ss environment permitted the expression of the Friend tumor phenotype, while interaction with the Fv-2rr environment allowed normal repopulation (i.e., hemopoietic stem cell self-renewal and differentiation). Thus, Fv-2 mediates resistance to the outgrowth of leukemia cells at the level of the hemopoietic environment. |
| Databáze: | OpenAIRE |
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