Expression and role of granulocyte macrophage colony-stimulating factor receptor (GM-CSFR) and granulocyte colony-stimulating factor receptor (G-CSFR) on Ph-positive acute B lymphoblastic leukemia

Hematology. 2018 Sep;23(8):439-447. doi: 10.1080/10245332.2018.1426540. Epub 2018 Jan 17.

Abstract

Objective: We observed that ph + ALL patients administrated with recombinant human G-CSF (rhG-CSF) after intense chemotherapy have presented a trend of disease relapse. Thus, we aim to thoroughly investigate the expression and role of GM-CSFR and G-CSFR on ph + ALL patients.

Method: SUP-B15, BALL-1 and primary leukemia cells were used in this study. Transcript levels were analyzed by quantitative PCR while cell viability was measured using a CCK-8 assay. Flow cytometry was used to assess the different stages of cell cycle.

Results: We found that the mRNA expression levels of GM-CSFR and G-CSFR were higher in patients with ph + ALL, as well as in SUP-B15 cells. rhG-CSF was also observed to promote the viability of SUP-B15 cells while inversely inhibiting BALL-1 cell viability. In addition, we also determined that rhG-CSF (100 ng/ml) decreased the sensitivity of SUP-B15 cells to imatinib and nilotinib, while the results were exactly the contrary for dasatinib.

Conclusion: We demonstrated high expression levels of GM-CSFR and G-CSFR, as well as their promotable role for viability in ph + ALL cells. We further found that rhG-CSF influenced the sensitivity of SUP-B15 cells to TKIs.

Keywords: G-CSFR; GM-CSFR; TKI; cell cycle; ph + ALL.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Male
  • Neoplasm Proteins / biosynthesis*
  • Philadelphia Chromosome*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Receptors, Granulocyte Colony-Stimulating Factor / biosynthesis*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*

Substances

  • Neoplasm Proteins
  • Receptors, Granulocyte Colony-Stimulating Factor
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor