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Megakaryocyte growth and development factor ameliorates carboplatin-induced thrombocytopenia in mice
T R Ulich1, J del Castillo, S Yin
1Amgen Inc., Thousand Oaks, CA 91320, USA.
Abstract:
Megakaryocyte growth and development factor (MGDF) administered intraperitoneally (IP) to mice causes a dose-dependent thrombocytosis accompanied by a decrease in mean platelet volume. MGDF increases the number of megakaryocytes in the bone marrow and spleen. MGDF does not affect the circulating number of leukocytes. Carboplatin, a chemotherapeutic agent that causes thrombocytopenia in humans, administered to mice as a single IP injection at a nonlethal dose causes a significant, but reversible thrombocytopenia. The carboplatin-induced thrombocytopenia is accompanied by an increase in circulating endogenous MGDF that precedes the return of circulating platelets to a normal level. MGDF mRNA is constitutively present in the liver. After carboplatin treatment, hepatic MGDF mRNA does not increase in concordance with circulating MGDF. Circulating soluble MGDF receptor levels (c-mpl) do not change significantly during the course of carboplatin-induced thrombocytopenia. MGDF injected IP once daily beginning 1 day after injection of carboplatin reverses carboplatin-induced thrombocytopenia in a dose-dependent fashion. The normalization of circulating platelet numbers in carboplatin plus MGDF-treated mice is accompanied by a normalization of megakaryocyte numbers in the bone marrow. In conclusion, MGDF, by increasing the number of marrow megakaryocytes and circulating platelets is an effective therapy for carboplatin-induced thrombocytopenia in mice.
Insights
Megakaryocyte growth and development factor (MGDF) effectively reverses carboplatin-induced thrombocytopenia in mice. This study shows MGDF therapy increases platelet production by boosting megakaryocyte numbers, offering a potential treatment for low platelet counts.
Area of Science:
- Hematology
- Pharmacology
- Oncology
Background:
- Carboplatin chemotherapy can cause thrombocytopenia (low platelet count).
- Megakaryocyte growth and development factor (MGDF) is involved in platelet production.
- Endogenous MGDF levels increase during recovery from carboplatin-induced thrombocytopenia.
Purpose of the Study:
- To investigate the therapeutic potential of MGDF in reversing carboplatin-induced thrombocytopenia in mice.
- To elucidate the mechanism by which MGDF influences platelet production and megakaryocyte proliferation.
Main Methods:
- Mice were treated with carboplatin to induce thrombocytopenia.
- MGDF was administered intraperitoneally (IP) to assess its effect on platelet recovery.
- Changes in platelet counts, megakaryocyte numbers, and MGDF levels were monitored.
Main Results:
- Carboplatin induced reversible thrombocytopenia in mice.
- MGDF administration dose-dependently reversed carboplatin-induced thrombocytopenia.
- MGDF treatment increased megakaryocyte numbers in bone marrow and spleen, leading to normalized platelet counts.
Conclusions:
- MGDF is an effective therapy for carboplatin-induced thrombocytopenia in mice.
- MGDF promotes platelet production by increasing megakaryocyte proliferation.
- This suggests a potential therapeutic strategy for chemotherapy-induced thrombocytopenia.