Dataset Information

Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia.

ABSTRACT: Background:Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) is a novel regulator of histone H3 acetylation and promotes leukemogenesis in acute myeloid leukemia (AML). However, its prognostic value in AML remains unclear. Methods:In this study, we evaluated the prognostic significance of ANP32A expression using two independent large cohorts of cytogenetically normal AML (CN-AML) patients. Multivariable analysis in CN-AML group was also presented. Based on the ANP32A expression, its related genes, dysregulation of pathways, interaction network analysis between microRNAs and target genes, as well as methylation analysis were performed to unveil the complex functions behind ANP32A. Results:Here we demonstrated overexpression of ANP32A was notably associated with unfavorable outcome in two independent cohorts of CN-AML patients (OS: P=0.012, EFS: P=0.005, n=185; OS: P=0.041, n=232), as well as in European Leukemia Net (ELN) Intermediate-I group (OS: P=0.018, EFS: P=0.045, n=115), National Comprehensive Cancer Network (NCCN) Intermediate Risk AML group (OS: P=0.048, EFS: P=0.039, n=225), and non-M3 AML group (OS: P=0.034, EFS: P=0.011, n=435). Multivariable analysis further validated ANP32A as a high-risk factor in CN-AML group. Multi-omics analysis presented overexpression of ANP32A was associated with aberrant expression of oncogenes and tumor suppressor, up/down-regulation of metabolic and immune-related pathways, dysregulation of microRNAs, and hypomethylation on CpG island and 1st Exon regions. Conclusions:We proved ANP32A as a novel, potential unfavorable prognosticator and therapeutic target for AML.

SUBMITTER: Huang S

PROVIDER: S-EPMC7186738 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia.

Huang Sai S Huang Zhi Z Ma Chao C Luo Lan L Li Yan-Fen YF Wu Yong-Li YL Ren Yuan Y Feng Cong C

Annals of translational medicine 20200301 6

<h4>Background</h4>Acidic leucine-rich nuclear phosphoprotein-32A (<i>ANP32A</i>) is a novel regulator of histone H3 acetylation and promotes leukemogenesis in acute myeloid leukemia (AML). However, its prognostic value in AML remains unclear.<h4>Methods</h4>In this study, we evaluated the prognostic significance of <i>ANP32A</i> expression using two independent large cohorts of cytogenetically normal AML (CN-AML) patients. Multivariable analysis in CN-AML group was also presented. Based on the ...[more]

PMID: 32355789

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Project description:Accumulating evidence highlights natural killer (NK) cell parameters as potential prognostic factors in cancer patients, which provides a strong rationale for developing therapeutic strategies aiming at restoring NK cell. However, reaching this point warrants better characterization of tumor-induced NK cell alterations. Our group recently reported heterogeneous NK maturation in acute myeloid leukemia (AML) patients. However, the clinical significance of such observations remained to be assessed on a larger cohort of patients. NK maturation based on expression of CD56, CD57, and KIR was assessed by flow cytometry in newly diagnosed AML patients (N = 87 patients from GOELAMS-LAM-IR-2006 multicenter trial). Clinical outcome was evaluated with regard to NK maturation profiles. Unsupervised integrated analysis of NK maturation markers confirmed the existence of three distinct groups of patients [hypomaturation (24.1%), intermediate maturation (66.7%), and hypermaturation (9.2%)]. In univariate analysis, significant differences in overall survival (OS) (P = 0.0006) and relapse-free survival (RFS) (P < 0.0001) were observed among these different groups. Patients with hypomaturation profile had reduced OS, with 3-year OS rates of 12.5 vs 57.1 and 57.4% for patients with intermediate and hypermaturation, respectively. Consistently, patients with hypomaturation profile had reduced RFS, with 3-year RFS rates of 0 vs 52.6 and 73.3% for patients with intermediate and hypermaturation, respectively. In multivariate Cox regression models, NK hypomaturation remained significantly associated with reduced OS and RFS, independent of other factors [hazard ratio (HR) = 4.15, P = 0.004 and HR = 8.23, P = 0.003, respectively]. NK maturation defects were further explored by mass cytometry and revealed that NK hypomaturation profile is associated with a reduced frequency of memory-like NK cells. In conclusion, besides classical alterations of NK triggering and inhibitory receptors expression in AML, we confirm that the homeostasis of NK maturation can be modified in the context of AML, notably with a deep maturation blockade in almost 10% patients.

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Dataset Information

Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia.

Publications

Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia.

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