Clinical Significance of Low Expression of LncRNA CASC15 in Acute Myeloid Leukemia with NPM1 Mutations / 中国实验血液学杂志

AbstractObjective: To identify the expression and methylation patterns of lncRNA CASC15 in bone marrow (BM) samples of acute myeloid leukemia (AML) patients, and further explore its clinical significance.@*METHODS@#Eighty-two de novo AML patients and 18 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the expression and methylation data of CASC15. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of CASC15 expression to identify AML. The patients were divided into CASC15high group and CASC15low group by X-tile method, and the prognostic value of CASC15 was identified by Kaplan-Meier method and univariate and multivariate Cox regression analysis.@*RESULTS@#The expression level of CASC15 was significantly decreased in BM cells of AML patients compared with healthy donors (P<0.001). ROC curve analysis suggested that CASC15 expression might be a potential biomarker to discriminate AML from controls. The expression of CASC15 was high at the early stage of hematopoiesis, and reached a peak at the stage of multipotent progenitors differentiation, then decreased rapidly, and was at a range of low level fluctuations in the subsequent process. Among FAB subtypes, CASC15 expression in M0 was significantly higher than that in M1-M7. Clinically, CASC15low patients were more likely to have NPM1 mutations than CASC15high patients (P=0.048), while CASC15high patients had a significantly higher frequency of IDH1 and RUNX1 mutations (P=0.021 and 0.014, respectively). Moreover, CASC15low group had a shorter overall survival (OS) in patients with NPM1 mutations. Furthermore, multivariate analysis confirmed that CASC15 expression was a significant independent risk factor for OS in NPM1 mutated AML patients. In addition, CASC15 methylation level in BM samples of AML patients was significantly decreased compared with healthy donors. Patients with CASC15 high methylation had poor OS and disease-free survival.@*CONCLUSION@#The expression of CASC15 is decreased in AML, and low CASC15 expression may predict adverse prognosis in AML patients with NPM1 mutations. Moreover, CASC15 methylation level in AML is significantly decreased, and high CASC15 methylation may predict poor prognosis in AML.

Methylation of miR-378 in Chronic Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the methylation status of miR-378 promoter in chronic myeloid leukemia (CML) and to analyze its clinical significance.</p><p><b>METHODS</b>The unmethylation level of miR-378 gene promoter in bone marrow mononuclear cells of 25 healthy donors and 53 patients with CML was detected by using real-time quantitative methylation-specific PCR (RQ-MSP).</p><p><b>RESULTS</b>The hypomethylation of miR-378 gene promoter was found in 17/53 (32.1%) patients, but only in 1/25 (4.0%) of controls. The difference between the two groups was very statistically significant (P < 0.01). The frequency of miR-378 unmethylation in CML patients at chronic phase (CP), accelerated phase (AP) and blastic phase (BP) was 35.0% (14/40), 40.0% (2/5), and 12.5% (1/8), respectively. However, there were no significant differences in the unmethylation level of miR-378 among CML patients at different sexes, stages and karyotypes. No significant differences could be observed in age, white blood cell counts, platelet count, hemoglobin level and BCR/ABL1 transcript level (P > 0.05). CONCLUDSION: The miR-378 hypomethylation is a common molecular event in CML, especially at chronic or accelerated phases.</p>