As a rate-limiting enzyme for the serine biosynthesis pathway (SSP) in the initial step, phosphoglycerate dehydrogenase () is overexpressed in many different tumors, and pharmacological or genetic inhibition of promotes antitumor effects. In the present research, by analyzing several acute myeloid leukemia (AML) datasets in the Gene Expression Omnibus (GEO), we identified prognosis-related genes and constructed a multigene signature by univariate, multivariate Cox regression and LASSO regression. Subsequently, the multigene signature was confirmed through Cox, Kaplan-Meier, and ROC analyses in the validation cohort. Moreover, acted as a risk factor and was correlated with inferior overall survival. We further analysed other datasets and found that was overexpressed in AML. Importantly, the expression of was higher in drug-resistant AML compared to drug-sensitive ones. experiments showed that inhibition of induced apoptosis and reduced proliferation in AML cells, and these antitumor effects could be related to the / signaling pathway by the noncanonical or nonmetabolic functions of . In summary, we constructed a twenty-gene signature that could predicate prognosis of AML patients and found that may be a potential target for AML treatment.