The t(8;21)(q22;q22) translocation is the most common chromosomal translocation in acute myeloid leukemia (AML), and it gives rise to acute myeloid gene 1 (AML1)-myeloid transforming gene 8 (ETO)-positive AML, which has a relatively favorable prognosis. However, the molecular mechanism related to a favorable prognosis in AML1-ETO-positive AML is still not fully understood. Our results show that the AML1-ETO fusion protein triggered activation of early growth response gene l (EGR1) by binding at AML1-binding sites on the EGR1 promoter and, subsequently, recruiting acetyltransferase P300, which is known to acetylate histones. However, AML1-ETO could not recruit DNA methyltransferases and histone deacetylases; therefore, EGR1 expression was affected by histone acetylation but not by DNA methylation. Both transcription and translation of EGR1 were higher in AML1-ETO-positive AML cell lines than in AML1-ETO-negative AML cell lines, owing to acetylation. Furthermore, when AML1-ETO-positive AML cell lines were treated with C646 (P300 inhibitor) and trichostatin A (histone deacetylase inhibitor), EGR1 expression was significantly decreased and increased, respectively. In addition, treatment with 5-azacytidine (methyltransferase inhibitor) did not cause any significant change in EGR1 expression. Overexpression of EGR1 inhibited cell proliferation and promoted apoptosis, and EGR1 knockout promoted cell proliferation. Thus, EGR1 could be a novel prognostic factor for a favorable outcome in AML1-ETO-positive AML. The results of our study may explain the molecular mechanisms underlying the favorable prognosis in AML1-ETO-positive AML.

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Background: Mismatch repair-proficient (pMMR) colorectal cancers (CRCs) are thought to be primarily resistant to immune checkpoint inhibitor (ICI) monotherapy. However, recent clinical trials have reported that early-to-mid stage (non-metastatic) CRC responds well to ICI monotherapy. We hypothesized that the efficacy of immunotherapy is linked to a series of gene expression profiles that can characterize the pMMR CRC disease stage.Methods: Using the Cancer Genome Atlas (TCGA) CRC data sets, we first investigated transcriptomic features that continuously changed (were continuously upregulated or downregulated) with pMMR CRC disease-stage progression. We defined these gene sets as stage-associated genes. The deconvolution algorithm then enriched these genes with the dynamic changes in the cell type populations of the CRC tumor microenvironment (TME). Finally, the stage-associated genes were cross-referenced to the current transcriptome profile data on ICI treatment of pMMR CRC, which revealed the gene set specifying an effective pMMR tumor response.Results: In total, 774 genes were found to increase in expression and 845 genes to decrease in expression as the stage increased. Using deconvolution methods, we discovered 2 major disease stage-associated alterations in the cellular composition of pMMR CRCs, including changes in cell types involved in host immune responses and tumor cell metastasis. The central memory CD8+ T cell population decreased as the pMMR CRC disease stage increased, but the endothelial cell populations associated with proliferation and metastasis increased. Using a different cell type annotation set (LM22), we discovered that as the disease progressed, M1 macrophages and CD8+ T cells decreased in the TME. In mismatch repair-deficient patients with CRC, however, such a decrease was not observed. Finally, we identified 27 signature genes that can be used to assess ICI efficacy in treatment-naïve patients with pMMR CRC. Conclusions:The current study sought to identify the underlying molecular mechanisms, pathways, and cell landscapes that explain why early-to-mid stage pMMR CRC responds well to ICI treatment. This analysis might be valuable for the selection of patients who might benefit from immunotherapeutic strategies.

With the changes in people's dietary life, the incidence and mortality of colon cancer have risen sharply. Invasive metastasis of colon cancer is the main reason affecting the prognosis. Therefore, it is very important to study the molecular mechanism of SDF-1/CXCR4 and integrin αvβ6 in liver metastasis of colon cancer. Floating cells were used to detect the appearance of β6, and the relationship between SDF-1/CXCR4 and the molecular mechanism of colon cancer redirection was analyzed. Use immunohistochemistry to detect the appearance of SDF-1/CXCR4 and αvβ6 protein, and combine the data with clinical-pathological data for statistical analysis. Experimental data showed that the positive expression rates of αvβ6 protein in well-differentiated and poorly differentiated colon cancer tissues were 21.4% and 30.6%, respectively, and the difference was statistically significant (P<0.01). The results show that the appearance of SDF-1/CXCR4 in colon cancer cells (CCC) has nothing to do with the type of cancer cells, and increases with the decrease of cell differentiation. This has a great relationship with the classification of the clinical TNM disease stage. The later the disease stage, the higher the expression level. The αvβ6 has a strong correlation with the invasion and metastasis of colon cancer and can be used as a criterion for judging liver metastasis and prognosis.

<b><i>Introduction:</i></b> The purpose of this study was to analyze the difference in clinical and aortic morphological features between the bovine aortic arch and normal aortic arch in patients with acute type B aortic dissection (aTBAD). <b><i>Methods:</i></b> A total of 133 patients diagnosed with aTBAD were retrospectively collected. Based on aortic arch morphology, they were divided into the bovine aortic arch group (<i>n</i> = 20) and the normal aortic arch group (<i>n</i> = 113). Aortic morphological features were assessed on computed tomographic angiography. Clinical and aortic morphological features were then compared between the bovine aortic arch and normal aortic arch groups. <b><i>Results:</i></b> Patients in the bovine aortic arch group were significantly younger and with higher weight and BMI than the normal aortic arch group (<i>p</i> &lt; 0.001, <i>p</i> = 0.045, and <i>p</i> = 0.016, respectively). The total aortic length in the bovine aortic arch group was significantly shorter than that in the normal aortic arch group (<i>p</i> = 0.039). The tortuosity of descending thoracic aorta, the tortuosity of descending aorta, and the angulation of aortic arch were significantly lower in the bovine aortic arch group (<i>p</i> = 0.004, <i>p</i> = 0.015, and <i>p</i> = 0.023, respectively). The width of descending aorta, the height of aorta arch, and the angle of ascending aorta were significantly smaller in the bovine aortic arch group (<i>p</i> = 0.045, <i>p</i> = 0.044, and <i>p</i> = 0.042, respectively). <b><i>Conclusion:</i></b> When the aTBAD occurred, patients with bovine aortic arch were prone to be younger and with higher BMI than those with normal aortic arch. The aortic curvature and the total aortic length were lower in patients with bovine aortic arch.