Value of SQLE Expression in Prognostic Evaluation of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the relationship between the expression level of SQLE and the prognosis of patients with acute myeloid leukemia (AML) through large sample data.@*METHODS@#The data of genome, transcriptome, gene chip expression, and clinical information were statistically analyzed in multiple cohorts of AML patients with large samples.@*RESULTS@#It was found that the expression level of SQLE gene in tumor cells of AML patients was significantly higher than that of healthy controls (P=0.001). In the three AML corhort, the SQLE high expression group showed a worse therapeutic outcome (OS, P=0.009, P=0.0001, P=0.006; EFS, P=0.005, P=0.001). The unvariate and multivariate survival prognosis analysis indicated that the high expression of SQLE suggests lower event-free survival rate (EFS, HR=1.551, P<0.05) and overall survival rate (OS, HR=1.484, P<0.05). At the same time, it was also found that among different risk subgroups, the expression of SQLE in high risk group was higher (P<0.001, P=0.01), while the patients with high SQLE expression, who received allogeneic HSCT, had longer overall survival time (P=0.006).@*CONCLUSION@#The up-regulation SQLE expression suggests a poor prognosis for the patients with AML.

Epigenetic Silencing of Eyes Absent 4 Gene by Acute Myeloid Leukemia 1-Eight-twenty-one Oncoprotein Contributes to Leukemogenesis in t(8;21) Acute Myeloid Leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The acute myeloid leukemia 1 (AML1)-eight-twenty-one (ETO) fusion protein generated by the t(8;21)(q22;q22) translocation is considered to display a crucial role in leukemogenesis in AML. By focusing on the anti-leukemia effects of eyes absent 4 (EYA4) gene on AML cells, we investigated the biologic and molecular mechanism associated with AML1-ETO expressed in t(8;21) AML.</p><p><b>METHODS</b>Qualitative polymerase chain reaction (PCR), quantitative reverse transcription PCR (RT-PCR), and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines. Different plasmids (including mutant plasmids) of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4. Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4. Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region. The influence of EYA4 gene in the cell proliferation, apoptosis, and cell clone-forming ability was detected by the technique of Cell Counting Kit-8, flow cytometry, and clonogenic assay.</p><p><b>RESULTS</b>EYA4 gene was hypermethylated in AML1-ETO+ patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells, compared to HL-60 and SKNO-1-siA/E cells, respectively. We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA4 gene by binding at AML1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases. Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AML1-ETO+ cell lines. We also found EYA4 transfection increased apoptosis of Kasumi-1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control, respectively.</p><p><b>CONCLUSIONS</b>Our study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene. In addition, we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML1-ETO+ t (8;21) AML.</p>

FLT3 gene overexpression and its clinical significance in acute myeloid leukemia with AML1/ETO fusion gene positive / 中国实验血液学杂志

This study was aimed to investigate the expression levels of FLT3 gene in AML-M2 patients carrying AML1/ETO fusion gene, and analyze its relation with clinical and laboratorial features and prognosis. RQ-PCR method was used to detect the expression level of FLT3 in bone marrow of 21 AML-M2 patients with AML1/ETO(+). The correlation of the expression level of FLT3 with clinical features, other laboratorial examinations and disease prognosis were analyzed. The results showed that gene expression level of FLT3 (FLT3 gene/ reference gene) in patients at initial diagnosis were 1.65%-261.5%. The expression level of FLT3 over 35% was defined as high expression group (12 cases) , while the expression level below 35% was defined as low expression group (9 cases) . The proportion of patients with extramedullary infiltration in high expression group was higher than that in low expression group (25% vs 0%, P = 0.2286). The proportion of patients at initial diagnosis with white blood cell count > 10×10(9)/L in high expression group was higher than that in low expression group (66.67% vs 22.22%), but there was no statistical significance (P = 0.0805). No significant difference was observed at the age (P = 0.1369) and the rate of bone marrow blasts (P = 0.6923) between the above mentioned two groups. The differences in complete remission rate (66.67% vs 88.89%, P = 0.3383), the relapse rate (66.67% vs 22.22%,P = 0.0805) and the mortality rate (50% vs 22.22%, P = 0.3666) between the two group were not significant, but there was a clear trend that the low expression group has a higher CR rate and a lower relapse rate and mortality rate. It is concluded that FLT3 gene high expression in AML-M2 patients with AML1/ETO(+) have a higher rate of relapse and hence poor prognosis. Therefore, detection of FLT3 expression level in routine clinical practice is important for patient's risk stratification, prognostic evaluation and effective treatment selection.