title: Prevention of chemotherapy-induced anemia and thrombocytopenia by constant administration of stem cell factor.
abstract: OBJECTIVE
  Chemotherapy-induced apoptosis of immature hematopoietic cells is a major cause of anemia and thrombocytopenia in cancer patients. Although hematopoietic growth factors such as erythropoietin and colony-stimulating factors cannot prevent the occurrence of drug-induced myelosuppression, stem cell factor (SCF) has been previously shown to protect immature erythroid and megakaryocytic cells in vitro from drug-induced apoptosis. However, the effect of SCF in vivo as a single myeloprotective agent has never been elucidated.
  
  
  METHODS
  The ability of SCF to prevent the occurrence of chemotherapy-induced anemia and thrombocytopenia was tested in a mouse model of cisplatin-induced myelosuppression. To highlight the importance of maintaining a continuous antiapoptotic signal in immature hematopoietic cells, we compared two treatment schedules: in the first schedule, SCF administration was interrupted during chemotherapy treatment and resumed thereafter, whereas in the second schedule, SCF was administered without interruption for 7 days, including the day of chemotherapy treatment.
  
  
  RESULTS
  The administration of SCF to cisplatin-treated mice could preserve bone marrow integrity, inhibit apoptosis of erythroid and megakaryocytic precursors, prevent chemotherapy-induced anemia, and rapidly restore normal platelet production. Treatment with SCF increased the frequency of Bcl-2/Bcl-XL-positive bone marrow erythroid cells and sustained Akt activation in megakaryocytes. Myeloprotection was observed only when SCF was administered concomitantly with cisplatin and kept constantly present during the days following chemotherapy treatment.
  
  
  CONCLUSIONS
  SCF treatment can prevent the occurrence of chemotherapy-induced anemia and thrombocytopenia in mice, indicating a potential use of this cytokine in the supportive therapy of cancer patients.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Bartucci
authors.forename: Rosanna
authors.initials: R
authors.lastname: Dattilo
authors.forename: Daniela
authors.initials: D
authors.lastname: Martinetti
authors.forename: Matilde
authors.initials: M
authors.lastname: Todaro
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Zapparelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Virgilio
authors.forename: Mauro
authors.initials: M
authors.lastname: Biffoni
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
authors.forename: Ann
authors.initials: A
authors.lastname: Zeuner
mesh_terms: D000740:Anemia / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D001854:Bone Marrow Cells / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D004334:Drug Administration Schedule; D015672:Erythroid Precursor Cells / Q000187:drug effects; D005260:Female; D008533:Megakaryocytes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D019089:Stem Cell Factor / Q000008:administration & dosage*; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D019089:Stem Cell Factor; D002945:Cisplatin