Evidence that stem cell factor is involved in the rebound thrombocytosis that follows 5-fluorouracil treatment
Autor: | P, Hunt, K M, Zsebo, M M, Hokom, A, Hornkohl, N C, Birkett, J C, del Castillo, F, Martin |
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Rok vydání: | 1992 |
Předmět: |
Thrombocytosis
Mice Inbred BALB C Stem Cell Factor Platelet Count Gene Expression Nucleic Acid Hybridization Receptors Cell Surface Hematopoietic Cell Growth Factors Polymerase Chain Reaction Kinetics Mice Proto-Oncogene Proteins c-kit Bone Marrow Proto-Oncogene Proteins Mutation Animals Fluorouracil RNA Messenger Megakaryocytes |
Zdroj: | Blood. 80(4) |
ISSN: | 0006-4971 |
Popis: | The mechanisms responsible for 5-fluorouracil (5FU)-induced rebound thrombocytosis are not completely understood. SI/SI(d) mice, which do not undergo rebound thrombocytosis in response to 5FU, provide a genetic approach to the study of this phenomenon. Recent reports by several groups that the SI locus encodes a protein known variably as stem cell factor (SCF), mast cell growth factor, or kit ligand, suggests the possibility that the lack of wild-type SCF in SI/SI(d) mice is responsible for their defective response to 5FU-induced thrombocytopenia. It is shown in this report that SCF-treated SI/SI(d) mice are as capable as their wild-type littermates in undergoing rebound thrombocytosis. W/Wv mice, mutated at the locus encoding the SCF receptor, also do not undergo rebound thrombocytosis, but are not responsive to SCF treatment. In normal mice, it is shown by RNA solution hybridization that SCF mRNA expression is increased during the 5FU-induced platelet nadir period. It is also shown by autoradiography that maturing megakaryocytes express SCF receptors, and that in vivo administration of SCF significantly raises the numbers of megakaryocytes, as well as circulating platelet counts. Taken together, these data indicate that SCF may be an important regulator of platelet production under both normal and physiologically disturbed situations. |
Databáze: | OpenAIRE |
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