Dataset Information

Low expression of ACLY associates with favorable prognosis in acute myeloid leukemia.

ABSTRACT:

Background

Aberrant 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).

Methods

To 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.

Results

Low 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.

Conclusion

We found low ACLY expression is associated with favorable overall survival in AML patients.

SUBMITTER: Wang J

PROVIDER: S-EPMC6509777 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Low expression of ACLY associates with favorable prognosis in acute myeloid leukemia.

Wang Jinghan J Ye Wenle W Yan Xiao X Guo Qi Q Ma Qiuling Q Lin Fang F Huang Jiansong J Jin Jie J

Journal of translational medicine 20190510 1

<h4>Background</h4>Aberrant 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).<h4>Methods</h4>To 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 ...[more]

PMID: 31077215

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Project description:Adrenomedullin (ADM) is a hypotensive and vasodilator peptide belonging to the calcitonin gene-related peptide family. It is secreted in vitro by endothelial cells and vascular smooth muscle cells, and is significantly upregulated by a number of stimuli. Moreover, ADM participates in the regulation of hematopoietic compartment, solid tumors and leukemias, such as acute myeloid leukemia (AML). To better characterize ADM involvement in AML pathogenesis, we investigated its expression during human hematopoiesis and in leukemic subsets, based on a morphological, cytogenetic and molecular characterization and in T cells from AML patients. In hematopoietic stem/progenitor cells and T lymphocytes from healthy subjects, ADM transcript was barely detectable. It was expressed at low levels by megakaryocytes and erythroblasts, while higher levels were measured in neutrophils, monocytes and plasma cells. Moreover, cells populating the hematopoietic niche, including mesenchymal stem cells, showed to express ADM. ADM was overexpressed in AML cells versus normal CD34+ cells and in the subset of leukemia compared with hematopoietic stem cells. In parallel, we detected a significant variation of ADM expression among cytogenetic subgroups, measuring the highest levels in inv(16)/t(16;16) or complex karyotype AML. According to the mutational status of AML-related genes, the analysis showed a lower expression of ADM in FLT3-ITD, NPM1-mutated AML and FLT3-ITD/NPM1-mutated cases compared with wild-type ones. Moreover, ADM expression had a negative impact on overall survival within the favorable risk class, while showing a potential positive impact within the subgroup receiving a not-intensive treatment. The expression of 135 genes involved in leukemogenesis, regulation of cell proliferation, ferroptosis, protection from apoptosis, HIF-1α signaling, JAK-STAT pathway, immune and inflammatory responses was correlated with ADM levels in the bone marrow cells of at least two AML cohorts. Moreover, ADM was upregulated in CD4+ T and CD8+ T cells from AML patients compared with healthy controls and some ADM co-expressed genes participate in a signature of immune tolerance that characterizes CD4+ T cells from leukemic patients. Overall, our study shows that ADM expression in AML associates with a stem cell phenotype, inflammatory signatures and genes related to immunosuppression, all factors that contribute to therapy resistance and disease relapse.

Dataset Information

Low expression of ACLY associates with favorable prognosis in acute myeloid leukemia.

Background

Methods

Results

Conclusion

Publications

Low expression of ACLY associates with favorable prognosis in acute myeloid leukemia.

Similar Datasets

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