Granulocyte colony-stimulating factor enhances the in vitro cytotoxicity of gemtuzumab ozogamicin against acute myeloid leukemia cell lines and primary blast cells.

Abstract

OBJECTIVE To evaluate the effects of granulocyte colony-stimulating factor (G-CSF) on the in vitro sensitivity of acute myeloid leukemia (AML) cell lines and primary AML blast cells to gemtuzumab ozogamicin (GO). MATERIALS AND METHODS AML cell lines and primary blasts from 10 patients with AML were first incubated for 72 hours in the presence of G-CSF (5 or 100 ng/mL) and then exposed to increasing concentrations of GO (1-1,000 ng/mL) for an additional 72 hours. RESULTS Pretreatment with G-CSF translated into significant enhancement of GO-induced cytotoxicity in the GO-sensitive HL-60 and NB-4 cells. Conversely, the response of GO-insensitive KG-1a, TF-1, and K562 cells was unaffected by in vitro priming with G-CSF. In vitro exposure to G-CSF augmented GO-induced apoptosis in 7 of 10 primary AML samples and rendered blast cells from three refractory patients sensitive to killing effect of GO. The G-CSF-induced increase of the cytocidal activity of GO was independent of effects on the cell cycle and on the expression levels of CD33 antigen. Of potential interest, G-CSF induced dose-dependent inhibition of P-glycoprotein (P-gp/ABCB1) function in the GO-sensitive HL-60 and NB-4 cells and in blasts from three patients with AML that we tested. CONCLUSION Collectively, our findings point to G-CSF as a potential sensitizing agent that can be exploited therapeutically to improve the clinical efficacy of GO.

Statistics

020040020072008200920102011201220132014201520162017
Citations per Year

216 Citations

Semantic Scholar estimates that this publication has 216 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Rutella2006GranulocyteCF, title={Granulocyte colony-stimulating factor enhances the in vitro cytotoxicity of gemtuzumab ozogamicin against acute myeloid leukemia cell lines and primary blast cells.}, author={Sergio Rutella and Giuseppina Bonanno and Annabella Procoli and Andrea Mariotti and Mothanje Barbara Lucia and Anna Maria Contemi and Roberto Cauda and Luana Fianchi and Giovanni Scambia and Livio Pagano and Giuseppe Riccardo Leone}, journal={Experimental hematology}, year={2006}, volume={34 1}, pages={54-65} }