Author Correction: The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Publisher Correction: The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

MHC Class I Expression in Murine Fibroblast and Keratinocyte Cell Lines During the First Twenty-four Hours of Infection with Herpes Simplex Virus-1 (HSV-1)

The hypothesis of this study is: HSV-1 infection of murine fibroblasts and keratinocytes inhibits expression of MHC class I molecules during first 24 hours of infection. IFN-γ pretreatment of fibroblasts protected the cells from virus-induced inhibition of MHC class I expression, but did not protect keratinocytes. Herpesviruses are known for their ability to establish persistent infections. Herpesviruses exert many different ways to suppress host defense mechanisms. One such way is by down regulating expression of the major histocompatibility complex I (MHC I) molecules in infected cells. Epidermal cells such as keratinocytes are the major sites for herpes simplex virus type 1 (HSV-1) replication both in active primary and recurring herpes infection. In this study, murine keratinocyte cell lines (HEL-30 and PAM-212) were shown to be refractory to IFN-γ induction of an MHC class I expression to HSV-1 infection, while IFN-γ did induce MHC class I expression in murine fibroblast cell lines (L929 and A2R1). In the current study, using Image J analyses of immunocytochemical data, MHC class I expression decreased at 6, 12, and 24 hours after infection of L929 and A2R1 fibroblasts (p\u3c 0.001) with HSV-1 infection. The effect of IFN-γ on expression of MHC I molecules was evaluated in HSV-1-infected murine keratinocytes and fibroblasts at 24 hours after infection. In other studies, IFN-γ was found to protect the murine fibroblast cell line, L929 from the cytopathic effect of HSV-1 but was unable to protect murine keratinocyte cell lines (HEL-30 and PAM-212) from HSV-1 induced cytopathic effects (Frey et al., 2009). Immunofluorescent staining for expression of MHC class I molecules in IFN-γ treated and HSV-1 infected cells was performed using immunocytochemistry and flow cytometry. Only the fibroblast cell lines could be examined by both methods. Significant increases (p \u3c 0.001) in expression of MHC class I molecules were seen in both HSV-1 infected fibroblast cell lines after treatment with IFN-γ using both immunocytochemistry and flow cytometry. Since keratinocytes grow in clusters, immunocytochemistry was not used to evaluate their expression of the MHC class I molecules in HSV-1-infected and IFN-γ treated cells. Keratinocytes could be gently removed from the culture using cell stripper solution, and were then examined by flow cytometry for expression of MHC class I molecules. In both keratinocyte cell lines, significant decreases in expression levels of MHC class I molecules over baseline levels (p\u3c0.001) were observed after HSV-1 infection and IFN-γ treatment. In the current study, HSV-1 infection of murine fibroblasts and keratinocytes inhibited expression of MHC class I molecules during first 24 hours of infection. IFN-γ pretreatment of fibroblasts protected them from virus-induced inhibition of MHC class I expression, but did not protect keratinocytes. The refractoriness of keratinocytes to IFN-γ might be due to the expression of suppressor of cytokine synthesis-1 (SOCS-1) during HSV-1 infection as observed by the Frey et al., (2009)

Serum MicroRNA-155 in Acute Graft-Versus-Host-Disease (aGVHD)

Allogeneic hematopoietic stem cell transplant (alloHSCT) is a curative treatment for many hematologic malignancies. Unfortunately, about 30-50% of all recipients undergoing alloHSCT develop acute graft-versus-host-disease (aGVHD), which is associated with high morbidity and mortality [1,2]. Treatment of aGVHD involves the use of immune suppressive drugs such as high dose of steroids that leads to further immunosuppression and risk for opportunistic infections. Often patients are refractory to steroids therapy making the prognosis dismal. Thus, it is critical to identify robust biomarkers to detect aGVHD before onset of clinical symptoms so that therapeutic strategies can be implemented that may result in better treatment responses and less toxicity.&nbsp

A differentially expressed set of micrornas in cerebro-spinal fluid (CSF) can diagnose CNS malignancies

Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application.The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies.CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization.Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies.This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications

The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1 -mutated acute myeloid leukemia

Funder: U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics)Abstract: Long non-coding RNAs (lncRNAs) are important regulatory molecules that are implicated in cellular physiology and pathology. In this work, we dissect the functional role of the HOXB-AS3 lncRNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 is shown to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism, HOXB-AS3 regulates ribosomal RNA transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts

Author Correction: The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1 -mutated acute myeloid leukemia

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Author Correction: The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

An amendment to this paper has been published and can be accessed via a link at the top of the paper