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Etude des micro-ARNs sériques dans les leucémies aiguës myéloïdes : vers une meilleure compréhension épigénétique de la leucémogénèse et une nouvelle approche de l’évaluation pronostique

Estelle Pedrono 1, 2 
2 CRCINA-ÉQUIPE 7 - Innate Immunity and Immunotherapy
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
Abstract : Acute myeloid leukaemia (AML) is a malignant proliferation of progenitors blocked during myeloid differentiation. The karyotype of the leukemic blasts identified three distinct prognostic groups. Among the favourable risk cytogenetics AML include acute promyelocytic leukaemia (APL), and those with inv (16) or t (8; 21). Micro-RNAs are key players in hematopoiesis and are also involved in leukemogenesis of AML. They are very stable in serum and used as biomarkers in cancers. The aim of this thesis was to evaluate whether a genome-wide characterization of serum micro-RNAs possible to distinguish these three types of AML them as well as AML with normal karyotype (NK-AML); identify micro-RNAs circulating highly overexpressed in NK-AML compared to healthy subjects, for later use as markers of residual disease; and to better define the prognosis of NK-AML. Thus, we have identified a specific serum signing of LAP related to a deregulation of micro-RNAs located in the DLK1-DIO3 under the imprinting, in 14q32. These micro-RNAs whose origin was the leukemic blasts were correlated with known prognosis factors of APL. In addition, two micro-RNAs, miR-10a-3p and miR-196b-5p, distinguishing the NK-AML with inv (16)-AML or t (8; 21)-AML have been shown overexpressed in NK-AML with mutation NPM1 and / or FLT3-ITD. Finally the expression of these two micro-RNAs correlates withtranscriptional deregulation and DNA methylation affectingTALE and HOX genes. In conclusion, this study of serum microRNAs opens a new field of exploration to assess the prognosis in AML.
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Estelle Pedrono. Etude des micro-ARNs sériques dans les leucémies aiguës myéloïdes : vers une meilleure compréhension épigénétique de la leucémogénèse et une nouvelle approche de l’évaluation pronostique. Médecine humaine et pathologie. Université d'Angers, 2014. Français. ⟨NNT : 2014ANGE0017⟩. ⟨tel-01475345⟩

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