Long noncoding RNAs (lncRNAs) are a large family of noncoding RNAs that play a critical role in various normal bioprocesses as well as tumorigenesis. However, the expression patterns and biological functions of lncRNAs in acute leukemia have not been well studied. Here, we performed transcriptome-wide lncRNA expression profiling of acute myeloid leukemia (AML) patient samples, along with non-leukemia control hematopoietic samples. We found that lncRNAs were differentially expressed in AML samples relative to control samples. Notably, we identified that lncRNAs upregulated in AML (relative to the control samples) are associated with a lower degree of DNA methylation and a higher ratio of being bound by transcription factors such as SP1, STAT4, ATF-2 and ELK-1 compared with those downregulated in AML. Moreover, an enrichment of H3K4me3 and a depletion of H3K27me3 were observed in upregulated lncRNAs in AML. Expression patterns of three types of lncRNAs (antisense, enhancer and intergenic lncRNAs) have previously been characterized. Of the identified lncRNAs, we found that high expression level lncRNA LOC285758 is associated with the poor prognosis in AML patients. Furthermore, we found that LOC285758 regulates proliferation of AML cell lines by enhancing the expression of HDAC2, a key factor in carcinogenesis. Collectively, our study depicts a landscape of important lncRNAs in AML and provides novel potential therapeutic targets and prognostic markers for AML treatment.
von Willebrand disease (VWD), an inherited bleeding disorder caused by deficiency or dysfunction of von Willebrand factor (VWF) is diagnosed when a personal and often a family history of excessive mucocutaneous bleeding is present along with abnormal laboratory studies. An accurate assessment of hemorrhagic symptoms is key in suspecting VWD but presents a challenge especially in children due to overlap between normal and abnormal bleeding. Bleeding questionnaire (BQ) scores have been validated in adults and have recently been validated in children with VWD for assessing bleeding severity. However there is limited data supporting their use prospectively in healthy children with bleeding complaints. The objectives of this study were to obtain normative data from children and validate a pediatric BQ to determine the discriminative ability of its total score and its individual components for identifying children likely to have VWD.
Methods
The pediatric BQ was administered to 1281 multiethnic, healthy children between 30 days and 18 years of age presenting to a general pediatric office and to 35 children with VWD based on VWF antigen, activity and multimer pattern.
Results
When children with total BQ scores of 3 or more were predicted to have VWD, the sensitivity was 97.2%, the specificity was 97.1%, the positive predictive value was 48.6%, and the negative predictive value was 99.9%.
Conclusions
The pediatric BQ may help discriminate a significant bleeding history from otherwise trivial bleeding and may be integrated into the primary care algorithm for evaluating children suspected of having VWD.
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