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Conférence CRCT : Dr Camille Lobry Institut Gustave Roussy, Paris : Non-coding genome and epigenetic regulation of transcription in leukemia
27 mars 2020 @ 11:00 - 12:00
Acute Myeloid Leukemia (AML) is the most common acute leukemia diagnosed in adults and is accounted for approximately 25000 new diagnosed cases per year in Europe. Despite the use of chemotherapy and stem cell transplantation, AML has a dismal overall 5-year survival of 24% and almost 50% of AML patients relapse after treatment. Currently, there are no targeted therapies for this disease making the study of the molecular mechanisms of its induction and progression of biologic and clinical significance.To date most efforts in understanding AML induction and progression have focused on the protein-coding genome, which in humans represents less than 2% of all our genetic material. Non-coding regions in the genome play an important role in regulating gene transcription. These regions encompass insulators, enhancers and non-coding RNA. Recently, Super Enhancers (SE) have been characterized as single or group of enhancers with unusual strong enrichment for binding of transcriptional co-activators and strong modifications of histone tails. SE can be virtually defined in any cell type and tend to be highly cell type specific. The human transcriptome is composed not only of protein-coding mRNA, but also a significant proportion of non-coding RNA (ncRNA). This finding has challenged the central dogma of molecular biology as ncRNAs do not act as intermediates between DNA and peptide, but rather function as regulatory molecules. Long non-coding RNAs (lncRNA) have recently become an attractive area of study as whole-transcriptome data has shown that their cellular abundance may be similar or even higher than that of mRNA and their expression appears to be highly tissue specific. Importantly, one of the key functions of lncRNA is to target chromatin modifiers to specific loci. Leukemic cells often present with altered gene expression patterns and enhancer usage compared to their normal counterparts. particularly, se tend to be enriched around and control genes known to play oncogenic functions. also, several reports have implicated lncrnas in the regulation of oncogene and tumor suppressor transcription in cancer. therefore, understanding se and lncrna functions could help decipher complex coordinated gene expression programs that lead to oncogenesis.