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Avian monocytic leukemia cells release fibroblast growth factor: implications to associated myelofibrosis
Abstract:
The marrow of chicks with leukemia induced by avian 'myeloblastosis' virus (AMV) exhibited a 5-10-fold increase in the number of fibroblast colony-forming cells (CFU-F). The increased CFU-F correlated with a mild fibrosis which can be seen in the marrow of these animals. Fibroblast proliferation likely was not simply due to the presence of leukemic cells because addition of formaldehyde-fixed peripheral leukemic cells failed to initiate CFU-F growth. Conditioned medium (CM) from day-4 cultures of peripheral leukemic cells was markedly stimulatory to CFU-F growth. The stimulatory activity was not due to virus released from the leukemic cells as, (1) removal of virus by pelleting had no effect on the CM activity and (2) direct inoculation of CFU-F cultures with virus failed to stimulate CFU-F growth. Normal avian marrow macrophage monolayers also released high levels of a fibroblast growth factor and both the macrophage-derived and leukemic cell-derived factors were heat-labile (65 degrees, 30 min).
Insights
Avian myeloblastosis virus (AMV) leukemia in chicks increases fibroblast colony-forming cells (CFU-F) and causes mild marrow fibrosis. Leukemic cells release a heat-labile fibroblast growth factor, not the virus itself.
Area of Science:
- Hematology
- Oncology
- Virology
Background:
- Avian myeloblastosis virus (AMV) induces leukemia in chicks.
- Leukemia is characterized by abnormal cell proliferation in the bone marrow.
- Fibroblast colony-forming cells (CFU-F) are crucial for bone marrow stromal integrity.
Purpose of the Study:
- To investigate the cause of increased fibroblast colony-forming cells (CFU-F) in AMV-induced leukemia.
- To determine if leukemic cells or the virus itself stimulate fibroblast proliferation.
- To identify the source and nature of the fibroblast growth factor.
Main Methods:
- Induction of leukemia in chicks using AMV.
- Quantification of CFU-F in bone marrow.
- Culture of peripheral leukemic cells and analysis of conditioned medium (CM).
- Assay of CM for fibroblast growth-stimulating activity.
- Testing the role of virus and heat-labile factors.
Main Results:
- AMV-induced leukemia led to a 5-10 fold increase in CFU-F.
- Increased CFU-F correlated with mild bone marrow fibrosis.
- Conditioned medium from leukemic cells significantly stimulated CFU-F growth.
- Fibroblast growth factor activity was present in CM and released by normal macrophages.
- The stimulatory factor was heat-labile and not the AMV virus itself.
Conclusions:
- Leukemic cells in AMV-infected chicks release a heat-labile fibroblast growth factor.
- This factor, not the virus, drives the observed increase in CFU-F and associated fibrosis.
- Normal avian macrophages also produce a similar fibroblast growth factor.