Stem cell factor protects erythroid precursor cells from chemotherapeutic agents via up-regulation of Bcl-2 family proteins

Ruggero De Maria Marchiano, Ann Zeuner, Francesca Pedini, Michele Signore, Ugo Testa, Elvira Pelosi, Cesare Peschle

Risultato della ricerca: Contributo in rivistaArticolo in rivista

42 Citazioni (Scopus)

Abstract

Suppression of red blood cell production is a common complication of chemotherapy, causing anemia in a significant number of cancer patients. We have evaluated the sensitivity of human hematopoietic progenitors and erythroid precursor cells to chemotherapeutic drugs and found that probasophilic erythroblasts represent the stage of erythroid differentiation more vulnerable to the cytotoxic effects of myelosuppressive agents. Stem cell factor (SCF) supports proliferation and survival of early hematopoietic cells by binding to the c-kit receptor. In unilineage erythropoietic culture of CD34+ progenitors, short-term pretreatment of immature erythroid precursors with SCF results in protection from apoptosis induced by chemotherapeutic agents and restores normal proliferation and differentiation after removal of the cytotoxic stimulus. The levels of drug-induced caspase processing are significantly reduced in erythroblasts treated with SCF, indicating that activation of the c-kit receptor generates antiapoptotic signals acting before amplification of the caspase cascade. Accordingly, we found that SCF up-regulates Bcl-2 and Bcl-XL in erythroid precursors and that exogenous expression of these proteins protects erythroblasts from caspase activation and death induced by chemotherapeutic agents. These results suggest a possible mechanism for SCF-mediated protection of erythroid precursor cells from apoptosis and may contribute to devise new strategies for prevention and treatment of chemotherapy-induced anemia. © 2003 by The American Society of Hematology.
Lingua originaleEnglish
pagine (da-a)87-93
Numero di pagine7
RivistaBlood
Volume102
DOI
Stato di pubblicazionePubblicato - 2003

Keywords

  • Antineoplastic Agents
  • Apoptosis
  • Caspases
  • Cell Division
  • Drug Antagonism
  • Erythroid Precursor Cells
  • Hematology
  • Hematopoietic Stem Cells
  • Humans
  • Male
  • Proto-Oncogene Proteins c-bcl-2
  • Stem Cell Factor
  • Up-Regulation
  • bcl-X Protein

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