| Title | Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia |
| Authors | Huang, Sai Huang, Zhi Ma, Chao Luo, Lan Li, Yan-Fen Wu, Yong-Li Ren, Yuan Feng, Cong |
| Affiliation | Chinese Peoples Liberat Army Gen Hosp, Dept Hematol, First Med Ctr, Beijing 100853, Peoples R China Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA Peking Univ, Dept Hematol, Third Hosp, Beijing 100191, Peoples R China Chinese Peoples Liberat Army Gen Hosp, Dept Emergency, First Med Ctr, 28 Fuxing Rd, Beijing 100853, Peoples R China |
| Keywords | ACUTE LYMPHOBLASTIC-LEUKEMIA ADULT PATIENTS TARGET GENES IDENTIFICATION PROGNOSIS APOPTOSIS IMPACT MUTATION DISEASE ANP32A |
| Issue Date | Mar-2020 |
| Publisher | ANNALS OF TRANSLATIONAL MEDICINE |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/587500 |
| ISSN | 2305-5839 |
| DOI | 10.21037/atm.2020.02.54 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 |
