State Key Lab for Medical Genomics, Shanghai Institute of Hematology of Ruijin Hospital affiliated to SJTU School of Medicine has published the latest research results in the molecular therapy mechanism of As₂O₃ (commonly called as arsenic) in anti-APL activities, revealing that the oncoprotein PML-RAR is the direct target of the arsenic trioxide against APL. They discovered that As₂O₃ binds directly to cysteine residues in zinc fingers located within PML, which induces PML obligomerization, increases its interaction with the protein modifier(SUMO), resulting in enhanced SUMOylation and degradation. The degradation of the oncoprotein finally leads to the differentiation and apoptosis of leukemia cells. This finding is a big success in APL molecular targeted therapy, enriching the related theories and promoting the molecular targeted therapy in other kinds of leukemia and solid tumor. The breakthrough in this research is the crystallization of the united strength of organizations like Institute of Biochemistry and Cell Biology under SIBS (Shanghai Institute for Biological Sciences) of the CAS (the Chinese Academy of Sciences), National Synchrotron Radiation Laboratory and School of Life Sciences of University of Science and Technology of China.

Apart from its identification of the drug target of As₂O₃ against APL and explanation of the molecular mechanism, the profound significance of this research achievement lies especially in the following aspects: first, ATAR and arsenic trioxide bind to different targeted areas of the same oncoprotein to exert therapeutic effect and induce the differentiation and apoptosis of leukemia cells, which offers theoretical and practical evidence for the new tumor-treating strategy; second, arsenic, is an ancient drug used for over 2000 years in traditional Chinese medicine according to the historic records. The combination of modern scientific methods with the molecular mechanism of traditional medicine will promote Chinese scientists to explore and develop the traditional Chinese drugs; third, this research result is a multidisciplinary and interdisciplinary achievement made through the persistent and cooperative efforts of various national and international research institutes including Institute of Biochemistry and Cell Biology under SIBS of the CAS, Institute of High Energy Physics of the CAS, School of Life Sciences and National Synchrotron Radiation Laboratory of University of Science and Technology of China, Institute of Zoology of the CAS, the Sino-French Research Center for Life Sciences and Genomics, and University of Paris VII, etc. The research has been supported by National “863” Program, National “973” Program, National Natural Science Foundation of China, and Shanghai Special Fund for Major Science and Technology Programs, etc.