BackgroundCurrently, cytogenetic and genetic markers are the most important for risk stratification and treatment of patients with acute myeloid leukemia (AML). Despite the identification of many prognostic factors, relatively few have made their way into clinical practice. Therefore, the identification of new AML biomarkers is useful in the prognosis and monitoring of AML and contributes to a better understanding of the molecular basis of the disease. Homeobox (HOX) genes are transcription factors that lead to cell differentiation blockade and malignant self-renewal. However, the roles of HOX genes in AML are still not fully understood and need further exploration, which may provide new strategies for the prognosis and monitoring of AML.MethodsWe analyzed the RNA sequencing and clinical data from The Cancer Genome Atlas (TCGA), VIZOME, GSE13159, and GSE9476 cohorts. Analyses were performed with GraphPad 7, the R language, and several online databases. We applied quantitative polymerase chain reaction, Western Blotting, CCK8 cell proliferation assays, and flow cytometry to verify the conclusions of the bioinformatics analysis.ResultsWe identified HOXB5 as the only gene among the HOX family that was not only elevated in AML but also a significant prognostic marker in AML patients. HOXB5 was highly expressed in AML patients with NPM1, FLT3, or DNMT3A mutations and was expressed at the highest level in patients with NPM1-FLT3-DNMT3A triple-mutant AML. Gene Ontology analysis and gene set enrichment analysis revealed that HOXB5 showed a negative correlation with the myeloid cell differentiation signature and that the tumor necrosis factor/nuclear factor κB signaling pathway was involved in the molecular mechanism. Moreover, we performed in silico protein–protein interaction analysis and 450K TCGA DNA methylation data analysis and found that HOXB5 interacted with two HOX genes (HOXA7 and HOXB4) that were commonly regulated by DNA methylation levels.ConclusionHOXB5 is associated with the malignant development of AML and may be a treatment target and biomarker for AML prognosis prediction.
Abnormality of the chromosomal karyotype is one factor causing poor prognosis in patients with lymphoma. Here, in the analysis of the abnormal karyotype of lymphoma patients, the three smallest overlapregions were found, in which MYCT1 was located. MYCT1 was first cloned by our research team as tumor suppressor gene, but studies related to the occurrence and development of lymphoma have not been reported. In this study, we found MYCT1 could inhibit proliferation and promote cell cycle arrest in diffuse large B-cell lymphoma cells. Moreover, we demonstrate that MYCT1 represses RUNX1 transcription by binding MAX. The findings provide clues and a basis for in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma.
Background Fatty acid metabolism has been reported to play important roles in the development of acute myeloid leukemia (AML), but there are no prognostic signatures composed of fatty acid metabolism-related genes. As the current prognostic evaluation system has limitations due to the heterogeneity of AML patients, it is necessary to develop a new signature based on fatty acid metabolism to better guide prognosis prediction and treatment selection. Methods We analyzed the RNA sequencing and clinical data of The Cancer Genome Atlas (TCGA) and Vizome cohorts. The analyses were performed with GraphPad 7, the R language and SPSS. Results We selected nine significant genes in the fatty acid metabolism gene set through univariate Cox analysis and the log-rank test. Then, a fatty acid metabolism signature was established based on these genes. We found that the signature was as an independent unfavourable prognostic factor and increased the precision of prediction when combined with classic factors in a nomogram. Gene Ontology (GO) and gene set enrichment analysis (GSEA) showed that the risk signature was closely associated with mitochondrial metabolism and that the high-risk group had an enhanced immune response. Conclusion The fatty acid metabolism signature is a new independent factor for predicting the clinical outcomes of AML patients.
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