Phenylarsine Oxide Can Induce Degradation of PLZF-RARα Variant Fusion Protein of Acute Promyelocytic Leukemia.
Liaqat HussainYasen MaimaitiyimingLi De SuQian Qian WangHua NaranmanduraPublished in: Chemical research in toxicology (2019)
PLZF-RARα is the second most frequent variant acute promyelocytic leukemia (APL) fusion protein that ranks after PML-RARα in APL. However, PLZF-RARα is resistant to current front line APL treatments including all transretinoic acid (ATRA), arsenic trioxide (ATO), and chemotherapy (i.e., Idarubicin). Herein, we for the first time report that phenylarsine oxide (PAO) could effectively induce PLZF-RARα variant fusion protein degradation through ubiquitin proteasome degradation pathway by apoptosis, which indicates that PAO might be a potential candidate for the treatment of PLZF-RARα variant APL. Given that, this study highlights the potential benefit of arsenic-organometallic compound PAO in APL treatment.
Keyphrases
- liver failure
- acute myeloid leukemia
- bone marrow
- drinking water
- respiratory failure
- oxidative stress
- heavy metals
- small molecule
- combination therapy
- drug induced
- intensive care unit
- risk assessment
- squamous cell carcinoma
- cell proliferation
- signaling pathway
- rectal cancer
- climate change
- acute respiratory distress syndrome