〔Abstract〕 Objective To explore the effect of glutamine transporter ASCT2 on myeloproliferative neoplasms(MPN)induced by SHP2 activation mutation, and to observe whether ASCT2 inhibitor l-glutamyl-4-nitroaniline(GPNA) can inhibit the progression of myeloproliferative neoplasms. Methods By constructing MPN mice model induced by Ptpn11E76 K/+activated mutation, the cell proliferation ability, amino acid and glutamic acid content, intracellular glycolysis of normal mice and mutant mice were analyzed, and the expression of ASCT2 protein and energy stress were compared. The mice were treated with ASCT2 inhibitor(GPNA), and ASCT2 protein and energy stress were compared between mutant mice and treated groups. The expression of p-mTOR and related proteins in the energy stress pathway and the rescue effect of the disease were detected. Results Ptpn11E76 K/+Mx1-Cre+activated mutant mice had high expression of glutamic acid,ASCT2 protein and strong cell proliferation ability; ASCT2 inhibitor decreased the progression of myeloproliferative neoplasms. Conclusion The expression level of ASCT2 is closely related to the pathogenesis of myeloproliferative neoplasms induced by SHP2 activated mutation. Inhibition of ASCT2 can effectively decrease the morbidity of myeloproliferative neoplasms, suggesting that ASCT2 may be an effective target for treating this type of disease.