Loss of ZNF215 imprinting is associated with poor five-year survival in patients with cytogenetically abnormal-acute myeloid leukemia

Ming-Yu Yang; Pai-Mei Lin; Chao-Hui Yang; Ming-Luen Hu; I-Ya Chen; Sheng-Fung Lin; Cheng-Ming Hsu

doi:10.1016/j.bcmd.2021.102577

Loss of ZNF215 imprinting is associated with poor five-year survival in patients with cytogenetically abnormal-acute myeloid leukemia

Blood Cells Mol Dis. 2021 Sep:90:102577. doi: 10.1016/j.bcmd.2021.102577. Epub 2021 May 26.

Authors

Ming-Yu Yang¹, Pai-Mei Lin², Chao-Hui Yang¹, Ming-Luen Hu³, I-Ya Chen⁴, Sheng-Fung Lin⁵, Cheng-Ming Hsu⁶

Affiliations

¹ Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan; Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
² School of Medicine for International Students and Department of Nursing, I-Shou University, Taiwan.
³ Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan; Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
⁴ Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan.
⁵ Division of Hematology and Oncology, Department of Internal Medicine, E-Da Hospital, Taiwan. Electronic address: shlin@cc.kmu.edu.tw.
⁶ Department of Otolaryngology Head and Neck Surgery, Chiayi Chang Gung Memorial Hospital, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taiwan. Electronic address: scm0031@cgmh.org.tw.

PMID: 34091126
DOI: 10.1016/j.bcmd.2021.102577

Abstract

Genomic imprinting is a form of epigenetic regulation and imprinted genes are silenced in a parental-specific manner. Imprinting is associated with various human diseases and cancers, but its roles in leukemogenesis remains elusive. In this study, the expression of a panel of 16 human imprinted genes was investigated using real-time quantitative polymerase chain reaction and 8 of them were further validated in 114 patients newly diagnosed with cytogenetically abnormal-acute myeloid leukemia (CA-AML) and 85 healthy subjects. Our results demonstrated upregulated expression of 8 imprinted genes (C15orf2, COPG2, H19, IGF2, PEG3-AS1, PRIM2, SLC22A3 and ZNF215) was observed in patients with CA-AML (p < 0.001). Patients' survival days were negatively correlated with the expression levels of H19 (p = 0.024), PGE3-AS1 (p = 0.038), and ZNF215 (p = 0.012). Multivariate logistic regression analysis further revealed the expression level ZNF215 can be used as a predictor for five-year survival for patients with CA-AML (p = 0.009) with a hazard ratio of 0.870 (95.0% confident interval: 0.784-0.965). Our results demonstrated that loss of imprinting of imprinted genes is critical for the leukemogenesis of AML under CA condition, and loss of ZNF215 imprinting is associated with poor five-year survival of patients with CA-AML.

Keywords: Cytogenetically abnormal-acute myeloid leukemia; Five-year survival; Genomic imprinting; Imprinted genes; ZNF215.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Chromosome Aberrations*
DNA-Binding Proteins* / biosynthesis
DNA-Binding Proteins* / genetics
Disease-Free Survival
Epigenesis, Genetic*
Female
Gene Expression Regulation, Leukemic*
Genomic Imprinting*
Humans
Leukemia, Myeloid, Acute* / genetics
Leukemia, Myeloid, Acute* / metabolism
Leukemia, Myeloid, Acute* / mortality
Male
Middle Aged
Neoplasm Proteins* / biosynthesis
Neoplasm Proteins* / genetics
Survival Rate

Substances

DNA-Binding Proteins
Neoplasm Proteins
ZNF215 protein, human