PML NBs switch from liquid-like to gel-like structures upon ATO
- VernacularTitle:Арсенийн триоксид (ATO)-ийн нөлөөгөөр pml бөөмийн биет (NB) шингэн төст хэлбэрээс гель төст бүтэц рүү шилждэг болох нь
- Author:
Sainjargal Ayush
1
;
Selenge Erdenechimeg
1
;
Javkhlan Bold
2
;
Hua Naranmandura
3
;
Bold Sharav
1
Author Information
1. Graduate School, Mongolian University of Pharmaceutical Sciences, Ulaanbaatar, Mongolia
2. Graduate School of Gunma University, Gunma, Japan
3. Institute of Pharmacology & Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
- Publication Type:Journal Article
- Keywords:
joint project;
PML;
ATO;
therapy
- From:
Mongolian Pharmacy and Pharmacology
2026;28(1):5-11
- CountryMongolia
- Language:Mongolian
-
Abstract:
Introduction:This research work was carried out as a joint project between the People’s Republic of China and
Mongolia. Mongolian contract number is CHN-2022/278, Chinese contract number is YS2021YFE010725. The title of the project is “The underlying mechanism of the synergistic effect of Arsenic Trioxide and Interferon Alpha on the treatment of Arsenic Resistant Acute Promyelocytic Leukemia”. The main executing organisation of Mongolia is the Mongolian Academy of Medical Sciences, and the project implementing organisation of the Chinese is Zhejiang University School of Medicine, and the People’s Hospital of Hangzhou Medical College, China.
PML nuclear bodies (NB) are disrupted in PML-RARα–driven acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) cures 70% of patients with APL, driving PML-RARα degradation and NB reformation. In non-APL cells, arsenic binding to PML also amplifies NB formation. Yet, the actual molecular mechanism(s) involved remain elusive.
Methods:PML and PML-RARα condensate dynamics were examined using live-cell time-lapse imaging, confocal
and STED super-resolution microscopy, and FRAP analysis in GFP-tagged PmlKO MEFs before and after arsenic trioxide (ATO) treatment.
Here, we establish that PML NBs display some features of liquid–liquid phase separation and that ATO induces a gel like transition. PML fusion to RARα altered its distribution in the nucleus, as GFP-PML-RAR α localised into many tiny dots with diam diameter below 100 nm in PmlKO MEFs. The basal dynamics of GFP-PML-RARα at these microdots were increased compared with PML at NBs, with a t1/2 of 1.37 minutes and, importantly, no immobile fraction. Here again, ATO treatment drastically decreased PML RARα exchange rates, closer to the dynamics of PML. Thus, ATO therapy drives the gel-like transition of both PML- or PML-RARα–driven condensates.
Conclusion:These findings show that arsenic trioxide (ATO) converts both PML and PML-RARα condensates
from a liquid-like, highly dynamic state into a gel-like, immobilized structure, revealing a key biophysical mechanism underlying ATO’s therapeutic action in APL.
- Full text:2026080123294934376MPPJ-2026-28(1)-5-11.pdf
