Abstract
BackgroundAberrant metabolism is a hallmark of cancer cells. Recently, ATP citrate-lyase (ACLY) expression was demonstrated as an independent predictor of clinical outcome in solid tumors. However, no systematic study was conducted to explore the prognostic impact of ACLY on acute myeloid leukemia (AML).MethodsTo assess the prognostic value of ACLY transcript, we conducted a study with a discovery and validation design. We measured ACLY transcript by real-time quantitative PCR in 274 AML patients, and validated the prognostic value in the two independent cohorts using published data. Meta-analysis of gene-expression profile and inhibition ACLY expression in leukemia cell lines were conducted to help us understand the biological insight of low ACLY expression.ResultsLow ACLY expression is less common amongst AMLs with DNMT3A mutations, but coexisted in double allele CEBPA mutations. Moreover, low ACLY expression is associated with favorable overall survival in AML patients and is involved in multiple pathways. These results are also validated in two independent cohorts of AML patients. Moreover, ACLY silencing induces proliferation arrest in THP-1 and MOLM-13 leukemia cell lines.ConclusionWe found low ACLY expression is associated with favorable overall survival in AML patients.
Highlights
Aberrant metabolism is a hallmark of cancer cells
We provide several critical pathways associated with low ATP citrate-lyase (ACLY) expression, and demonstrate that inhibition of ACLY led to proliferation arrest in THP-1 and MOLM-13 leukemia cell lines
Patient characteristics In this study, ACLY expressions were analyzed in bone marrow samples from 274 adult patients with newly diagnosed acute myeloid leukemia (AML)
Summary
ATP citrate-lyase (ACLY) expression was demonstrated as an independent predictor of clinical outcome in solid tumors. No systematic study was conducted to explore the prognostic impact of ACLY on acute myeloid leukemia (AML). To the best of our knowledge, there is not yet a study to exclusively evaluate the clinical significance and biological insights of ACLY expression in AML. To address this unresolved issue, we evaluated the prognostic value of ACLY expression in our AML patients and validated the result against two published cohorts of AML patients. ACLY expression in AML may act as a prognostic predictor and potential therapy target in the near future
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