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Abnormal splenic megakaryopoiesis in MPSV-induced myeloproliferative disease
M C Le Bousse-Kerdiles1, R Fernandez-Delgado, F Smadja-Joffe
1INSERM U 268, Hôpital Paul Brousse, Villejuif, France.
Abstract:
The myeloproliferative sarcoma virus (MPSV) induces a murine myeloproliferative syndrome characterized by an erythromyelemia, an anemia, a thrombocytopenia associated with a myeloproliferation in the spleen and a splenic and medullar fibrosis. We have used the in-vitro plasma clot technique to measure megakaryocytic precursors in the spleen and bone-marrow of MPSV-infected mice. We report that megakaryocytic colonies are increased, in number (X75), in concentration (X9) and in size, in the spleen but not in the bone-marrow of neoplastic mice. Furthermore, these splenic precursors are hypersensitive to growth factors present in the anemic mouse serum used in the culture system. These data show that the thrombocytopenia observed in the MPSV-induced neoplasia does not result from a lack of megakaryocyte precursors, but rather from an excess of megakaryocyte destruction. This ineffective splenic megakaryopoiesis associated with the presence of a massive splenic fibrosis make the MPS-induced neoplasia a suitable model for studying the perturbation of megakaryopoiesis in myeloproliferative syndrome associated with fibrosis.
Insights
Myeloproliferative sarcoma virus (MPSV) causes spleen fibrosis and increased megakaryocyte precursors in mice. Thrombocytopenia results from precursor destruction, not deficiency, making this a model for myeloproliferative syndromes.
Area of Science:
- Hematology
- Oncology
- Virology
Background:
- Myeloproliferative sarcoma virus (MPSV) induces a murine myeloproliferative syndrome.
- This syndrome is characterized by erythremic myelosis, anemia, thrombocytopenia, splenomegaly, and fibrosis.
Purpose of the Study:
- To investigate megakaryocytic precursor levels in MPSV-infected mice.
- To determine the cause of thrombocytopenia in this model.
Main Methods:
- Utilized the in-vitro plasma clot technique.
- Quantified megakaryocytic colony-forming units in spleen and bone marrow of MPSV-infected mice.
Main Results:
- Megakaryocytic colonies significantly increased in number, concentration, and size within the spleen, but not bone marrow.
- Splenic megakaryocyte precursors exhibited hypersensitivity to growth factors in anemic mouse serum.
- Thrombocytopenia was attributed to excessive megakaryocyte destruction rather than precursor deficiency.
Conclusions:
- The MPSV-induced murine model displays ineffective splenic megakaryopoiesis and significant splenic fibrosis.
- This model is suitable for studying megakaryopoiesis perturbations in myeloproliferative neoplasms associated with fibrosis.