Aging-related genes related to the prognosis and the immune microenvironment of acute myeloid leukemia

Abstract

Background: Acute myeloid leukemia (AML), one of the most common malignancies of the hematologic system, has progressively increased in incidence.Aging is present in both normal tissues and the tumor microenvironment. However, the relationship between senescence and AML prognosis is still not elucidated.Methods: In this study, RNA sequencing data of AML were obtained from TCGA, and prognostic prediction models were established by LASSO-Cox analysis. 2Differences in immune infiltration between the different risk groups were calculated using the CIBERSORT and ESTIMATE scoring methods. The KEGG and GO gene enrichment and GSEA enrichment were also used to enrich for differential pathways between the two groups. Subsequently, this study collected bone marrow samples from patients and healthy individuals to verify the differential expression of uncoupling protein 2 (UCP2) in different populations. Genipin, a UCP2 protein inhibitor, was also used to examine its effects on proliferation, cell cycle, and apoptosis in AML cell lines in vitro.Results: It showed that Aging-related genes (ARGs) expression was correlated with prognosis. And there was a significant difference in the abundance of immune microenvironment cells between the two groups of patients at high risk and low risk. Subsequently, UCP2 expression was found to be elevated in AML patients. Genipin inhibits UCP2 protein and suppresses the proliferation of AML cell lines in vitro. Conclusion:ARGs can be used as a predictor of prognosis in AML patients. Moreover, suppressing UCP2 can reduce the proliferation of AML cell lines, alter their cell cycle and promote apoptosis in vitro.

Histone marks enable formation of immiscible phase-separated chromatin compartments

“…Several studies have shown that overexpression of CBX7 and loss of H3K9me3 are related to the emergence of AML [19][20][21] , so we analyzed the transcriptome of mCherry-CBX7 3T3 cell lines. We detected up-regulation of leukemia-related genes [22][23][24][25] , and down-regulation of genes related to nucleosome assembly and genomic stability (Extended Data Fig. 6a-c).…”