Prevention of chemotherapy-induced anemia and thrombocytopenia by constant administration of stem cell factor

Ruggero De Maria Marchiano, Monica Bartucci, Rosanna Dattilo, Daniela Martinetti, Matilde Todaro, Giuseppina Zapparelli, Antonio Di Virgilio, Mauro Biffoni, Ann Zeuner

Risultato della ricerca: Contributo in rivistaArticolo in rivista

18 Citazioni (Scopus)

Abstract

Purpose: 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. Experimental Design: 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. ©2011 AACR.
Lingua originaleEnglish
pagine (da-a)6185-6191
Numero di pagine7
RivistaClinical Cancer Research
Volume17
DOI
Stato di pubblicazionePubblicato - 2011

Keywords

  • Anemia
  • Animals
  • Antineoplastic Agents
  • Bone Marrow Cells
  • Cancer Research
  • Cisplatin
  • Drug Administration Schedule
  • Erythroid Precursor Cells
  • Female
  • Megakaryocytes
  • Mice
  • Mice, Inbred C57BL
  • Oncology
  • Stem Cell Factor
  • Thrombocytopenia

Fingerprint

Entra nei temi di ricerca di 'Prevention of chemotherapy-induced anemia and thrombocytopenia by constant administration of stem cell factor'. Insieme formano una fingerprint unica.

Cita questo