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Background The liver-enriched microRNA-122 ( miR-122 ) plays a crucial role in pathogenesis of hepatocellular carcinoma (HCC) with prognostic value. Recently, miR-122 was also found to be related to many other cancers besides HCC. However, less study determined miR-122 expression and its clinical significance in acute myeloid leukemia (AML). Methods Real-time quantitative PCR was performed to detect the level of bone marrow (BM) miR-122 in de novo AML patients. The clinical significance of miR-122 expression in AML was further investigated. Results Among whole-cohort AML, lower expression of BM miR-122 was associated with male patients, higher hemoglobin and favorable-karyotypes ( P  = 0.038, 0.006, and 0.038, respectively). Among cytogenetically normal AML (CN-AML), lower expression of BM miR-122 was correlated with DNMT3A wild type ( P  = 0.043). Moreover, patients with lower expression of BM miR-122 presented lower complete remission (CR) rate and shorter overall survival (OS) than those with higher expression of BM miR-122 in CN-AML ( P  = 0.025 and 0.013, respectively). Cox regression analyses further confirmed the prognostic value of BM miR-122 expression in CN-AML ( P  = 0.024). In follow-up patients, BM miR-122 expression level in CR time was increased compared to diagnosis time, and was returned to primary level when in relapse time again ( P  = 0.062 and 0.049, respectively). Conclusions Our findings indicated that lower expression of BM miR-122 acted as an independent risk factor for OS in CN-AML. [ABSTRACT FROM AUTHOR]

Abstract Objective SOX7 downregulation caused by its promoter methylation was associated with poor survival in several types of human solid tumors. However, the pattern of SOX7 methylation and its clinical significance are less studied in hematological malignancies. Herein, we evaluated the methylation pattern of SOX7 in myelodysplastic syndrome (MDS) and determined its clinical implication in patients with MDS. Methods SOX7 methylation was determined by real-time quantitative methylation-specific PCR (RQ-MSP) in 99 MDS patients. Bisulfite sequencing PCR was applied to confirm the results of RQ-MSP. Results SOX7 methylation was detected in 55.6% of 99 patients but not in healthy donors. No correlation was found between SOX7 methylation and clinical parameters including patient age, gender, white blood cell count, hemoglobin, and platelet count. However, patients with SOX7 methylation harbored more U2AF1 mutation than patients without SOX7 methylation (P = 0.015). Kaplan-Meier curves indicated that the patients with SOX7 methylation presented reduced overall survival (OS) (P = 0.034). Furthermore, subgroup analysis indicated that SOX7 methylation was associated with poor OS in male patients (P = 0.034) and in patients older than 60 years (P = 0.019). According to the multivariate analysis, SOX7 methylation remained as an independent prognosis factor in MDS patients both as dichotomous (HR = 2.14, P = 0.041) and as continuous (HR = 1.55, P = 0.042) variable. Importantly, SOX7 methylation was significantly increased during progression from MDS to secondary acute myeloid leukemia (sAML). Conclusions Our findings demonstrated that SOX7 methylation conferred adverse prognosis in MDS patients and was associated with leukemia progression. [ABSTRACT FROM AUTHOR]

Background Somatic mutations in SETBP1 gene have recently been detected in hematologic malignancies. The present study aimed to explore the frequency and clinical correlations of SETBP1 mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Methods In this study, we used high-resolution melting analysis (HRMA) to detect the SETBP1 mutations in a cohort of 363 patients with AML or MDS. Results A total of 1.2% (3/249) of AML and 1.8% (2/114) of MDS patients were found with heterozygous SETBP1 mutations. In AML, patients with SETBP1 mutations showed higher hemoglobin ( P  = 0.004) and were more frequently recurrent in AML-M4 subtype ( P  = 0.034). All five SETBP1 mutated patients had normal karyotypes. The patients with SETBP1 mutations had significantly higher incidences of concurrent SRSF2 mutations ( P  = 0.002). HRMA could detect SETBP1 mutations with 5% sensitivity, obviously higher than 25% of Sanger sequencing. Conclusions We established a rapid, inexpensive, high-throughput and sensitive method to screen SETBP1 mutations. SETBP1 mutations were a rare molecular event in AML and MDS patients. [ABSTRACT FROM AUTHOR]

Activation of Wnt/β-catenin signaling played a crucial role in tumorigenesis, and β-catenin ( CTNNB1 ) overexpression has been identified in numerous solid tumors. The present study was designed to determine CTNNB1 expression and its clinical significance in Chinese de novo acute myeloid leukemia (AML) patients. Real-time quantitative PCR was carried out to detect the pattern of CTNNB1 expression in 140 AML patients and 46 controls. The level of CTNNB1 transcript in AML patients was significantly up-regulated compared with controls ( P <  0.001). CTNNB1 high patients showed significantly older age than CTNNB1 low patients ( P <  0.05). The frequency of high CTNNB1 expression was significantly observed in patients with intermediate/poor karyotypes. CTNNB1 high patients had a significantly lower complete remission (CR) rate than CTNNB1 low patients ( P  = 0.004). Among cytogenetically normal AML (CN-AML), CTNNB1 high patients presented significantly shorter overall survival (OS, P  = 0.004) and leukemia-free survival (LFS, P  = 0.038) than CTNNB1 low patients. Multivariate analysis confirmed that CTNNB1 expression was an independent prognostic factor for OS among CN-AML. Moreover, CTNNB1 expression level significantly decreased after CR stage ( P  = 0.032) and increased in relapsed stage ( P  = 0.015). Our findings suggest that CTNNB1 is overexpressed and confers a poor prognosis in AML, and could be used as a biomarker in monitoring disease recurrence. [ABSTRACT FROM AUTHOR]

Background Accumulating studies have linked the disruptions of microRNA-10 ( miR-10 ) to acute myeloid leukemia (AML) with NPM1 mutation. However, miR-10 expression and its clinical implication in AML remain poorly defined. Although a recent report showed high serum level of miR-10a was associated with adverse prognosis in AML, herein, we found bone marrow (BM) miR-10 overexpression was not a prognostic biomarker in AML. Methods BM miR-10 expression was examined by real-time quantitative PCR in BM mononuclear cells in 115 de novo AML patients and 45 controls. Results BM miR-10 ( miR-10a/b ) expression was significantly up-regulated in AML patients, and was positively correlated with each other. Overexpression of miR-10a was associated with lower percentage of BM blasts, whereas miR-10b overexpression tended to correlate with higher percentage of BM blasts. Importantly, miR-10a overexpression was significantly associated with FAB-M3/t(15;17) subtypes and NPM1 mutation, meanwhile, overexpression of miR-10b was correlated with NPM1 and DNMT3A mutations. However, miR-10a/b overexpression was not associated with complete remission rate, and did not have an impact on both leukemia free survival and overall survival time in non-M3 AML patients without NPM1 mutation. Conclusions BM miR-10 overexpression is associated with genetic events but not affects clinical outcome in AML. [ABSTRACT FROM AUTHOR]