Altered expression of imprinted genes in patients with cytogenetically normal‑acute myeloid leukemia: Implications for leukemogenesis and survival outcomes

Abstract

Genomic imprinting, an epigenetic mechanism that regulates gene expression from parental chromosomes, holds substantial relevance in multiple cancers, including hematopoietic malignancies. In the present study, the expression of a panel of 16 human imprinted genes in bone marrow samples from 64 patients newly diagnosed with cytogenetically normal-acute myeloid leukemia (CN-AML) were examined alongside peripheral blood samples from 85 healthy subjects. The validated findings of the present study revealed significant upregulation of seven genes [COPI coat complex subunit gamma 2 (COPG2), H19 imprinted maternally expressed transcript (H19), insulin like growth factor 2 (IGF2), PEG3 antisense RNA 1 (PEG3-AS1), DNA primase subunit 2 (PRIM2), solute carrier family 22 member 3 SLC22A3 and Zinc finger protein 215 (ZNF215)] in patients with CN-AML (P<0.001). Notably, the expression level of H19 exhibited an inverse association with the survival duration of the patients (P=0.018), establishing it as a predictive marker for two- and five-year survival in patients with CN-AML. Kaplan-Meier analysis demonstrated that patients with lower H19 expression had superior two- and five-year survival rates compared with those with higher H19 expression. The results of the present study highlighted the association between loss of imprinting and leukemogenesis in CN-AML, underscoring the significance of H19 imprinting loss as a prognostic indicator for unfavorable two- and five-year survival in CN-AML patients.

Keywords: H19 gene; cytogenetically normal-acute myeloid leukemia; five-year survival; imprinted genes; two-year survival.

Figure 1

Screening the expression of imprinted genes in patients with AML. The expression of 16 imprinted genes was screened in 25 patients with AML and 19 healthy subjects using reverse transcription-quantitative PCR. Expression of 8 imprinted genes was significantly upregulated in patients with AML. The difference in expression of imprinted genes between healthy subjects and patients with AML was evaluated by the Mann-Whitney test using values of -ΔCq [-(Cq of imprinted gene-Cq of ACTB gene)]. Data reported are median and range of -ΔCq. Higher-ΔCq values represent higher expression levels. Statistical significance at ^*P<0.05 and ^**P<0.001. AML, acute myeloid leukemia.

Figure 2

Validation of altered expression of imprinted genes in patients with CN-AML. The altered expression of imprinted genes was validated in patients with CN-AML using reverse transcription-quantitative PCR. Expression of the 7 imprinted genes was significantly upregulated in patients with CN-AML (n=64) compared with healthy subjects (n=85). The difference in expression of imprinted genes between healthy subjects and patients with CN-AML was evaluated by the Mann-Whitney test using values of -ΔCq [-(Cq of imprinted gene-Cq of ACTB gene)]. Data reported are median and range of -ΔCq Higher-ΔCq values represent higher expression levels. ^**P<0.001. CN-AML, cytogenetically-normal acute myeloid leukemia.

Figure 3

H19 expression as a potential predictor for survival in patients with CN-AML. (A) ROC curve demonstrating the predictive ability of H19 expression for two-year survival in patients with CN-AML. Patients with lower expression of H19 exhibited improved two-year survival. (B) Kaplan-Meier survival curve showing the two-year survival rates in patients with CN-AML with lower expression of H19 compared with those with higher H19 expression (log-rank P=0.006). (C) Kaplan-Meier survival curve displaying the five-year survival rates in patients with CN-AML with lower H19 expression compared with those with higher H19 expression (log-rank P=0.029). CN-AML, cytogenetically normal acute myeloid leukemia; AUC, area under the curve; CI, Confidence interval; ROC, receiver operating characteristic.