The mitochondrial transcription machinery genes are upregulated in acute myeloid leukemia and associated with poor clinical outcome

Abstract

BackgroundAcute myeloid leukemia (AML) is characterized by rapid growth of abnormal blasts that overcrowd normal hematopoiesis. Defective mitochondrial biogenesis has been implicated in AML, which we believe is partly due to the deregulation of the mitochondrial transcription machinery (MTM) genes influencing the expression of mitochondrial genes. Here, we aim to characterize MTM gene upregulation in AML. MethodsMolecular and clinical patient data were retrieved from several public AML datasets. Kaplan-Meier survival curves were used to compare overall survival between patients, while Mann–Whitney U's non-parametric and Fisher's exact test were used for comparing continuous and categorical variables, respectively. ResultsThe MTM genes TFB1M, TFB2M, TFAM, and POLRMT were upregulated in patients with AML compared with healthy donors. Upregulation of one or more of these genes was associated with higher percentage of peripheral blood blasts (P = 0.002), normal cytogenetic status (P = 0.027) and NPM1 mutations (P = 0.009). Additionally, patients with high expression of MTM genes (Z ≥ 1) had shorter median overall survival compared with low MTM gene expression (Z < 1) (months: 11.8 vs 24.1, P = 0.027; multivariate survival analysis Cox Proportional Hazards model, HR: 1.82 (1.22–2.70); p-value: 0.003). ConclusionThe mitochondrial transcriptional machinery is upregulated and associated with worse clinical outcome in patients with AML and may present a viable therapeutic target.