Key Features of the Paper
STUDY AIM
To establish whether organic arsenic species phenylarsine oxide (PAO) could induce the mutant PML-IV (A216V) protein solubility changes and degradation.
Methods
Three different PML protein variants (i.e., PML-IV, PML-V and mutant PML-A216V) were overexpressed in HEK293T cells and then exposed to PAO in time- and dose-dependent manners.
In order to confirm where PAO (or MMAIII ) induced PML protein solubility changes are dependent on cell death by cytotoxicity, high concentrations (e.g., 100 _ M) of adriamycin, a chemotherapeutic agent, was used to establish PML protein solubility changes.
Results
In this study, we found that can induce normal PML-IV and -V solubility changes, and PML-IV seems to be less sensitive to treatment than PML-V (Figure 1). Additionally, had no appreciable effects on induction ofsolubility changes of mutant PML (A216V), which is consistent with other published reports.
On the other hand, mutant PML (A216V) protein can form PML-NBs but it cannot be degraded by iAsIII , suggesting that formation of the PML-NBs is not a sufficient condition for mutant PML protein degradation.
Conclusion
The authors found that PAO is capable of inducing mutant PML protein solubility changes and degradation, suggesting that PAO is a considerable agent for relapsed/refractory APL. However, further investigation is needed to determine the dose level and toxicity of PAO in vivo and in vitro more carefully for clinical practices.