Osteopontin plays a unique role in resistance of CD34+/CD123+ human leukemia cell lines KG1a to parthenolide.

OBJECTIVES: To determine if parthenolide (PTL) is cytotoxic for leukemia-like KG1a cells and if it involves in certain molecular-mediated resistance, especially osteopontin (OPN).

METHODS: PTL/daunorubicin (DNR)-treated KG1a cells were examined for viability using MTT and colony-formation assay, and stained for apoptosis using AV/PI. The gene and protein expression were evaluated by qReal-time PCR and Western blotting analysis, respectively. OPN gene was inhibited by OPN siRNA. The cells were stained for various fractions using PE anti-CD34, FITC anti-CD38 and PerCP anti-CD123.

RESULTS: Cell viability and proliferation assay exhibited KG1a cells are relatively refractory to used concentrations of PTL. OPN mRNA and protein levels increased in response to PTL. Suppression of OPN with siRNA increased the cytotoxic effects of PTL on KG1a cells. PTL treatment and OPN siRNA suppression in KG1a cells resulted in a decrease of mRNA expression of AKT, mTOR, β-catenin, and Phosphatase and tensin homolog (PTEN). The sub-population cells of CD34(+) and CD123(+) from KG1a cells are enriched by PTL treatment.

CONCLUSION: Parthenolide in spite of the reduction in gene expression of AKT, mTOR or beta-catenin, stimulates the OPN expression in KG1a cells. The OPN expression pattern in KG1a cells could be compatible with CD34(+)/CD123(+) subtype enrichment by PTL which in turn implies OPN's unique role in resistance of cell populations characterized by CD34(+)/CD123(+) phenotype.