Priming with GM-CSF instead of G-CSF enhances CAG-induced apoptosis of acute monocytic leukemia cells in vitro

Cancer Chemother Pharmacol. 2019 Aug;84(2):265-273. doi: 10.1007/s00280-019-03857-8. Epub 2019 May 21.

Abstract

High expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor has been found in myelomonocytic or monocytic subtypes (M4/M5) of acute myeloid leukemia. Herein, we aimed to improve the effect of CAG [Ara-C, ACR, and G-CSF (granulocyte colony-stimulating factor)] regimen for acute monocytic leukemia by replacing G-CSF with GM-CSF. Results showed that the percentage of cells in S phase was higher with GM-CSF than with G-CSF treatment at 20 ng/mL (P < 0.05). When THP-1 and SHI-1 cells were primed with 20 ng/mL G-CSF or GM-CSF followed by Ara-C and ACR, cell proliferation rate in the CAGM (Ara-C, ACR, and GM-CSF) regimen was lower than in the CAG regimen (P < 0.05). Furthermore, CAGM regimen induced more obvious cell apoptosis than CAG regimen probably by reducing Bcl-2/Bax ratio (P < 0.05). Similar results were seen in primary cells from M5 patients. Collectively, our study suggests that priming with GM-CSF may be more effective than G-CSF in CAG regimen in acute monocytic leukemia.

Keywords: Acute monocytic leukemia; CAG; CAGM; Cell lines; Cytotoxicity; Primary cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Cell Line, Tumor
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Leukemia, Monocytic, Acute / drug therapy*
  • Male
  • Middle Aged

Substances

  • Granulocyte-Macrophage Colony-Stimulating Factor