RESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
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.
Asunto(s)
Leucemia Mieloide/genética , Mutación , Proteínas Nucleares/genética , ARN Largo no Codificante/genética , ARN Ribosómico/genética , Transcripción Genética , Enfermedad Aguda , Animales , Línea Celular Tumoral , Proliferación Celular , Células HEK293 , Humanos , Células K562 , Leucemia Mieloide/patología , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Nucleofosmina , Biosíntesis de Proteínas/genética , Células THP-1 , Trasplante HeterólogoRESUMEN
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.
Asunto(s)
Neoplasias del Sistema Nervioso Central/líquido cefalorraquídeo , Líquido Cefalorraquídeo/metabolismo , MicroARNs/líquido cefalorraquídeo , MicroARNs/genética , Biomarcadores/metabolismo , Biomarcadores de Tumor , Biopsia , Neoplasias Encefálicas/líquido cefalorraquídeo , Diagnóstico Diferencial , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Glioblastoma/líquido cefalorraquídeo , Humanos , Hibridación in Situ , MicroARNs/metabolismo , Nanotecnología/métodos , Estadificación de Neoplasias , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
The first transgenic mouse of the TCL1 oncogene was described more than 15 years ago, and since then, the overexpression of the gene in T- and B-cells in vivo has been extensively studied to reveal the molecular details in the pathogenesis of some lymphocytic leukemias. This review discusses the main features of the original TCL1 models and the different lines of research successively developed with particular attention to genetically compound mice and the therapeutic applications in drug development.
