CD312 Promotes Paediatric Acute Lymphoblastic Leukaemia Through GNA15‐Mediated Non‐Classical GPCR Signalling Pathway

ABSTRACT The bone marrow‐infiltrated immune microenvironment plays a crucial role in blood system diseases, such as leukaemia. In this study, we aimed to investigate the critical role of the immune microenvironment in the onset and progression of childhood acute lymphoblastic leukaemia (ALL). Through high‐throughput detection and screening of the GPCR database in the childhood ALL immune microenvironment, we identified CD312 as a candidate target. CD312 is associated with the distribution of Treg and CTL cells within the bone marrow immune microenvironment of ALL children. After CD312 knockdown, the proportion of the Treg subgroup in immune cells was significantly reduced, whereas the proportion of CTL subgroup cells was increased. CD312 exhibited good affinity with GNA15 in the transmembrane intracellular segment, and it could interact with GNA15. The BrdU staining assay revealed that the proliferation of leukaemia cells was enhanced in the CD312‐overexpressed CD3+ T cells group via the phosphorylation of ERK, JNK and p38, whereas it was decreased by GNA15 knockdown in the co‐culture system. In conclusion, our study suggests that CD312 fosters a suppressive immune microenvironment in the onset and progression of paediatric ALL through a GNA15‐mediated non‐classical GPCR signalling pathway.