Reduction of Platelets and Megakaryocytes in c-mpl-Deficient Mice
The ability to treat various forms of cancer is often limited by the ability of patients to tolerate the dosing and frequency of chemotherapeutic agents. This is mostly caused by a loss of cells of hematopoietic origin, specifically red blood cells, neutrophils, and platelets. This results in anemia, increased susceptibility to infections, and the potential for severe bleeding episodes. Currently, there are cytokines that have the potential to address the loss of some of these cell types. Erythropoietin (EPO) is very effective in stimulating the production of red blood cells and granulocyte colony-stimulating factor (G-CSF) stimulates neutrophil production, thus it is possible to combat the anemia and neutropenia with cytokines that are approved for use in humans (although many of the precise indications related to cancer therapy are still in clinical trials). The treatment of the associated thrombocytopenia remains more problematic. To date, it can only be addressed by platelet transfusions, which has its own associated risks. For many years researchers have sought for a cytokine with the ability to specifically stimulate platelet production in a manner similar to EPO stimulation of red blood cells or G-CSF stimulation of white cells. Several cytokines, IL-3, IL-6, and IL-11 (1,2), have been shown to stimulate platelet production but the increase is relatively modest and there are potential side effects as these cytokines are not specific for platelets and stimulate a variety of responses. Clinical trials are underway with these cytokines to determine their benefit in treating thrombocytopenic patients.
KeywordsDifferential Cell Count Bone Marrow Smear Hematopoietic Origin Receptor Ligand System Megakaryocyte Growth
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