Overexpression of ATP1B1 predicts an adverse prognosis in cytogenetically normal acute myeloid leukemia

Abstract

ATP1B1 encodes the Na,K-ATPase β subunit, a key regulator of the Na+ and K+ electrochemical gradients across the plasma membrane and an essential regulator of cellular activity. We used several microarray datasets to test the prognostic efficacy of ATP1B1 expression in cytogenetically normal acute myeloid leukemia (CN-AML). Within the primary cohort (n = 157), high ATP1B1 expression (ATP1B1high) was associated with shorter overall survival (OS) and event-free survival (EFS) (P = 0.0068, P = 0.0039, respectively). Similar results were also obtained in the European Leukemia Net (ELN) Intermediate-I genetic category (OS: P = 0.0035, EFS: P = 0.0007). Multivariable analyses confirmed ATP1B1high is an independent predictor of shorter OS (P = 0.042) and EFS (P = 0.035). Analysis of another CN-AML cohort confirmed that ATP1B1high is associated with shorter OS (P = 0.0046, n = 162). In addition, up-regulation of oncogenes/onco-microRNAs such as MYCN, CCND2, CDK6, KIT and miR-155, among others, was associated with ATP1B1high, which may be indicative of ATP1B1’s leukemogenicity. Our results may improve risk stratification and indicate new therapeutic targets for CN-AML.