inputtime：2022-08-22 17:10:31 From：Qilu Hospital
Recently, Prof. Ji Chunyan’s team from the Department of Hematology of Qilu Hospital of SDU, Prof. Li Jingxin’s team from School of Basic Medical Sciences of SDU, and Prof. Zhao Baobing’s team from School of Pharmaceutical Sciences of SDU jointly published a research result titled Inhibition of the m6A Reader IGF2BP2 as a Strategy against T-cell Acute Lymphoblastic Leukemia on Leukemia (Chinese Academy of Sciences(CAS) Journal ranking Q1, IF：12.883）, a prestigious journal in the field of hematology and tumor. This study revealed for the first time the cancer-promoting role of IGF2BP2, an m6A methylated "reading protein", in T-ALL, and screened and functionally identified small molecule inhibitors that specifically target IGF2BP2, providing new ideas for the targeted therapy of T-ALL. Prof. Ji Chunyan, Prof. Li Jingxin, and Prof. Zhao Baobing are co-corresponding authors. Feng Panpan, a doctoral student of the Department of Hematology, Qilu Hospital, and Chen Dawei, a doctoral student of the GIGA Institute of the University of Liege, Belgium are co-first authors. Qilu Hospital of Shandong University is the first corresponding author’s and the first author’s affiliation.
T-ALL is a malignant clonal disease of the hematopoietic system. Most patients develop primary drug resistance or relapse, and the prognosis is poor. Therefore, exploring the mechanism of reversal of drug resistance and new therapeutic targets is of critical significance clinically. The RNA-binding protein IGF2BP2 can act as an m6A methylated "reading protein" to regulate the expression of downstream target genes and mediate the occurrence and development of various malignant tumors, but its role in T-ALL is still unclear. This study firstly found that the expression of IGF2BP2 was significantly increased in T-ALL patients, and it was confirmed in vitro and in vivo that its high expression could promote the development and drug resistance of T-ALL. Through the combined analysis of iRIP-sequence and MeRIP-sequence sequencing, it was confirmed for the first time that IGF2BP2 can directly bind and regulate the expression of the cancer-promoting gene NOTCH1 in an m6A-dependent manner, thereby affecting the biological function of T-ALL cells. In addition, the team cooperated with the School of Pharmaceutical Sciences to screen the small molecule inhibitor JX5 that specifically targets IGF2BP2 using the virtual docking technology of protein molecules, and verified the direct binding effect of JX5 and IGF2BP2 protein and its Lethal toxicity on T-ALL cells in vitro. They also confirmed that JX5 can significantly delay tumor progression in T-ALL mice in vivo. This study is the first to elucidate the oncogene role and regulatory mechanism of IGF2BP2 in T-ALL, and identify small molecule inhibitors targeting IGF2BP2, providing a new target for the treatment of this disease.
Prof. Ji Chunyan's team has long been committed to basic and clinical research on leukemia, focusing on multidisciplinary integration, developing new technologies for precise diagnosis and treatment of leukemia, and focusing on transformation and applications. In recent years, Ji Chunyan has made many innovative achievements in the field of leukemia pathogenesis, multidrug resistance, targeted therapy and artificial intelligence precision diagnosis and treatment, and has received several grants from the National Natural Science Foundation of China (including major research programs), the Mount Tai Scholars Climbing Program and many provincial and ministerial projects. He has published over 100 SCI papers, authorized 2 national invention patents and 2 computer software copyrights. The main research results of "biological behavior abnormalities of leukemia and its reversal countermeasures" and "research, development and application of key technologies for precise diagnosis and treatment of leukemia" won the first prize of Science and Technology Progress Award of Shandong Province in 2012 and 2021 respectively.
Link：https://www.nature.com/articles/s41375-022-01651-9
