Recently, Professor Ji Chunyan’s team of the Department of Hematology of Qilu Hospital of Shandong University, published an article entitled “Homodimer-mediated phosphorylation of C/EBPα-p42 S16 modulates acute myeloid leukaemia differentiation through liquid-liquid phase separation” in Nature Communications (Chinese Academy of Sciences (CAS)District 1; 5-year average IF=17.0). The work revealed a mechanism that homodimer-mediated phosphorylation of C/EBPα modulates AML cell differentiation by LLPS, which provided a new insight for the treatment of the AML. Professor Ji Chunyan and Professor Lu Fei are co-corresponding authors of this article. Assistant researcher Wang Dongmei and researcher Sun Tao from the Department of Hematology of Qilu Hospital of Shandong University are co-first authors. Qilu Hospital of Shandong University is the first author’s and corresponding author’s affiliation.

AML is characterized by a differentiation arrest and an uncontrolled proliferation of malignant blasts. Despite advances in our understanding of disease mechanisms offering considerable effect for AML, the outcome of most AML patients remains poor. Thus, it is of great scientific significance and clinical application value to study the molecular mechanism of its occurrence, development and drug resistance, and to carry out accurate diagnosis and treatment of diseases and find new treatment strategies. CCAAT/enhancer-binding protein alpha (C/EBPα) is a basic-leucine zipper (bZIP) transcription factor and serves as a main regulator of myeloid differentiation and leukaemogenesis. This study systematically revealed C/EBPα regulates AML cell differentiation through liquid-liquid phase separation (LLPS), which can be disrupted by C/EBPα-p30. Mechanistically, homodimerization of C/EBPα mediated its phosphorylation at the novel phosphorylation site S16, which promoted LLPS and subsequent AML cell differentiation. Moreover, it confirmed that the liquid-liquid separation of regulating C/EBPα could significantly delay the pathogenesis of AML in mice, which provides an idea for the treatment of this disease.

Professor Ji Chunyan's team has been committed to basic and clinical research on leukemia and other malignant hematological diseases for a long time, devoting to the innovation and clinical transformation of basic research. At the same time, his team actively promote interdisciplinary integration and try to make a breakthrough in accurate diagnosis and treatment technology of leukemia. In recent years, Prof. Ji’s team has made many innovative achievements in the pathogenesis and drug resistance mechanism of leukemia, targeted therapy and accurate diagnosis and treatment of artificial intelligence, which have been funded by the National Natural Science Foundation of China (including major research projects), Mount Tai Scholars Climbing Program and many provincial and ministerial programs. The team has published more than 100 articles in high-level academic journals, including Nature Communications, Leukemia and Advanced Science. The main research results "R&D, Popularization and Application of Key Technologies for Accurate Diagnosis and Treatment of Leukemia" won the first prize of the Shandong Provincial Scientific and Technological Progress Prize in 2021.

Link：https://www.nature.com/articles/s41467-023-42650-3