Upregulation of Glutamic-Oxaloacetic Transaminase 1 Predicts Poor Prognosis in Acute Myeloid Leukemia

Abstract

One of the key features of acute myeloid leukemia (AML), a group of very aggressive myeloid malignancies, is their strikingly heterogenous outcomes. Accurate biomarkers are needed to improve prognostic assessment. Glutamate oxaloacetate transaminase 1 (GOT1) is essential for cell proliferation and apoptosis by regulating cell's metabolic dependency on glucose. It is unclear whether the expression level of <i>GOT1</i> has clinical implications in AML. Therefore, we analyzed the data of 155 AML patients with <i>GOT1</i> expression information from The Cancer Genome Atlas (TCGA) database. Among them, 84 patients were treated with chemotherapy alone, while 71 received allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both treatment groups, high <i>GOT1</i> expression was associated with shorter event-free survival (EFS) and overall survival (OS) (all <i>P</i> < 0.05). Multivariate analysis identified several independent risk factors for both EFS and OS in the chemotherapy-only group, including high <i>GOT1</i> expression, age ≥60 years, white blood cell count ≥15 × 10⁹/L, bone marrow blasts ≥70%, and <i>DNMT3A, RUNX1</i> or <i>TP53</i> mutations (all <i>P</i> < 0.05); but in the allo-HSCT group, the only independent risk factor for survival was high <i>GOT1</i> expression (<i>P</i> < 0.05 for both EFS and OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the genes related to <i>GOT1</i> expression were mainly concentrated in "hematopoietic cell lineage" and "leukocyte transendothelial migration" signaling pathways. Collectively, <i>GOT1</i> expression may be a useful prognostic indicator in AML, especially in patients who have undergone allo-HSCT.