XJTU Research Progress in Pathogenesis and Targeted Therapy of Leukemia
Recently, Professor Kong Guangyao from the National-Local Joint Engineering Research Center of Biodiagnostics &Biotherapy of XJTU Second Affiliated Hospital announced that, unlike acute myeloid leukemia, the Notch signaling pathway plays a key role as the oncogenein myeloproliferative neoplasm (MPN). The research used gene knock-in and knock-out mice, inhibited the Notch signaling pathway in the Kras-induced mouse model of leukemia, and found that after the down-regulation of Notch signaling pathway, MPN incidence was significantly reduced and the mice lived much longer. Further mechanism studies showed that the inhibition of the Notch signaling pathway could suppress activation of the ERK signaling pathway by up-regulating its negative regulator DUSP1. Additionally, it also inhibited oxidative phosphorylation of leukemia cells. More importantly, simultaneous inhibition of the ERK signaling pathway and oxidative phosphorylation had a better targeted killing effect on leukemia cells, which may be a potential target therapeutic strategy for MPN.
The research result was published online in Leukemia (IF=10.02),an authoritative journal in the leukemia field under the title "Downregulating Notch counteracts KrasG12D-induced ERK activation and oxidative phosphorylation in myeloproliferative neoplasm". Professor Kong Guangyao is the first author and corresponding author, and the Second Affiliated Hospital of XJTU is the institutional affiliation of the first author. Professor Zhang Jing from the University of Wisconsin is the co-author.