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 GOT1 has clinical implications in AML. Therefore, we analyzed the data of 155 AML patients with GOT1 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 GOT1 expression was associated with shorter event-free survival (EFS) and overall survival (OS) (all P < 0.05). Multivariate analysis identified several independent risk factors for both EFS and OS in the chemotherapy-only group, including high GOT1 expression, age ≥60 years, white blood cell count ≥15 × 109/L, bone marrow blasts ≥70%, and DNMT3A, RUNX1 or TP53 mutations (all P < 0.05); but in the allo-HSCT group, the only independent risk factor for survival was high GOT1 expression (P < 0.05 for both EFS and OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the genes related to GOT1 expression were mainly concentrated in “hematopoietic cell lineage” and “leukocyte transendothelial migration” signaling pathways. Collectively, GOT1 expression may be a useful prognostic indicator in AML, especially in patients who have undergone allo-HSCT.
Highlights
Acute myeloid leukemia (AML), the most common type of acute leukemia, is a clinically, genetically, and molecularly heterogeneous disease associated with uncontrolled proliferation and blocked differentiation of immature myeloid progenitors [1]
We found that overexpression of Glutamate oxaloacetate transaminase 1 (GOT1) is uniformly associated with poor survival in acute myeloid leukemia (AML) patients, regardless of the treatment modality they underwent; allo-HSCT might not abate its strong, detrimental effect on AML prognosis
A study demonstrated that one of the mechanisms of KRAS in inducing pancreatic ductal adenocarcinoma is by up-regulating GOT1 and inhibiting glutamate dehydrogenase 1 (GLUD1), reprogramming glutamine metabolism [11]
Summary
Acute myeloid leukemia (AML), the most common type of acute leukemia, is a clinically, genetically, and molecularly heterogeneous disease associated with uncontrolled proliferation and blocked differentiation of immature myeloid progenitors [1]. The choice of postremission strategy depends on AML risk stratification. The European LeukemiaNet (ELN) system is the most widely accepted risk stratification system in the postgenomic era. It heavily utilizes cytogenetic and molecular aberrations, such as FLT3-ITD, NPM1, CEBPA, RUNX1, TP53, and ASXL1 mutations [2]. Abnormal oncogene expressions have attracted more attention in recent years, with great potentials to be incorporated into a refined AML risk stratification system [3, 4]. High expressions of the secreted frizzled-related protein 2 (sFRP2) and docking protein 7 (DOK7) genes are associated with better outcome [5, 6], while high expressions of FHL2 and iASPP are associated with poor survival in AML [7]
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