Display options
Share it on

Cancer Cell Int. 2015 Dec 21;15:122. doi: 10.1186/s12935-015-0272-3. eCollection 2015.

Treatment with G-CSF reduces acute myeloid leukemia blast viability in the presence of bone marrow stroma.

Cancer cell international

Meritxell Nomdedeu, María Carmen Lara-Castillo, Amaia Etxabe, Josep María Cornet-Masana, Marta Pratcorona, Marina Díaz-Beyá, Xavier Calvo, María Rozman, Dolors Costa, Jordi Esteve, Ruth M Risueño

Affiliations

  1. Josep Carreras Leukaemia Research Institute, Campus Clínic-University of Barcelona, Rosselló 149-153, 08036 Barcelona, Spain ; Department of Hematology, Hospital Clínic, Barcelona, Spain.
  2. Josep Carreras Leukaemia Research Institute, Campus Clínic-University of Barcelona, Rosselló 149-153, 08036 Barcelona, Spain.
  3. Josep Carreras Leukaemia Research Institute, Campus Clínic-University of Barcelona, Rosselló 149-153, 08036 Barcelona, Spain ; Department of Hematology, Hospital Clínic, Barcelona, Spain ; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain ; Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.
  4. Josep Carreras Leukaemia Research Institute, Campus Clínic-University of Barcelona, Rosselló 149-153, 08036 Barcelona, Spain ; Department of Hematology, Hospital Clínic, Barcelona, Spain ; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
  5. Hematopathology Unit, Hospital Clínic, Barcelona, Spain.

PMID: 26696777 PMCID: PMC4687155 DOI: 10.1186/s12935-015-0272-3

Abstract

BACKGROUND: The resulting clinical impact of the combined use of G-CSF with chemotherapy as a chemosensitizing strategy for treatment of acute myeloid leukemia (AML) patients is still controversial. In this study, the effect of ex vivo treatment with G-CSF on AML primary blasts was studied.

METHODS: Peripheral blood mononuclear cells from AML patients were treated with G-CSF at increasing doses, alone or in co-culture with HS-5 stromal cells. Cell viability and surface phenotype was determined by flow cytometry 72 h after treatment. For clonogenicity assays, AML primary samples were treated for 18 h with G-CSF at increasing concentrations and cultured in methyl-cellulose for 14 days. Colonies were counted based on cellularity and morphology criteria.

RESULTS: The presence of G-CSF reduced the overall viability of AML cells co-cultured with bone marrow stroma; whereas, in absence of stroma, a negligible effect was observed. Moreover, clonogenic capacity of AML cells was significantly reduced upon treatment with G-CSF. Interestingly, reduction in the AML clonogenic capacity correlated with the sensitivity to chemotherapy observed in vivo.

CONCLUSIONS: These ex vivo results would provide a biological basis to data available from studies showing a clinical benefit with the use of G-CSF as a priming agent in patients with a chemosensitive AML and would support implementation of further studies exploring new strategies of chemotherapy priming in AML.

Keywords: AML; Chemotherapy priming; G-CSF

References

  1. Leukemia. 1999 Aug;13(8):1207-13 - PubMed
  2. Leukemia. 1987 Jan;1(1):1-8 - PubMed
  3. Blood. 1999 Apr 15;93(8):2478-84 - PubMed
  4. Expert Rev Hematol. 2011 Jun;4(3):271-83 - PubMed
  5. Nat Biotechnol. 2007 Nov;25(11):1315-21 - PubMed
  6. Blood. 1997 Dec 15;90(12):4710-8 - PubMed
  7. Blood. 2010 Jun 24;115(25):5131-6 - PubMed
  8. Br J Haematol. 1999 Oct;107(1):69-79 - PubMed
  9. J Leukoc Biol. 2003 May;73(5):630-8 - PubMed
  10. N Engl J Med. 1995 Jun 22;332(25):1678-83 - PubMed
  11. Science. 1986 Apr 4;232(4746):61-5 - PubMed
  12. Int J Biochem Cell Biol. 2009 Dec;41(12):2372-5 - PubMed
  13. Blood. 2012 Jun 7;119(23):5367-73 - PubMed
  14. Nat Med. 1997 Jul;3(7):730-7 - PubMed
  15. Blood. 1994 Apr 15;83(8):2086-92 - PubMed
  16. Blood. 2005 Jul 1;106(1):27-34 - PubMed
  17. Leuk Lymphoma. 1998 Jan;28(3-4):265-73 - PubMed
  18. Front Biosci. 2007 Jan 01;12:800-15 - PubMed
  19. N Engl J Med. 2003 Aug 21;349(8):743-52 - PubMed
  20. Blood. 2007 Oct 1;110(7):2276-85 - PubMed

Publication Types