Expression de GALIG, gène inducteur de la mort cellulaire, dans des cellules normales et pathologiques

Abstract : Embedded within the GALECTIN-3 gene, GALIG gene allows the production of 2 proteins, Galigins, which interact with autophagy proteins. Described as a pro-apoptotic gene, it is inhibited by Mcl-1, an anti-apoptotic protein. It is under-expressed in the bone marrow (BM) of patients with Acute Myeloid Leukemia (AML) M2, a pathology characterized by a differentiation blocking. During my thesis, I showed that the GALIG gene could be involved in myeloid differentiation. The expression of GALIG gene gradually increases in AML with the differentiation stage of the leukemic cell. In addition, although weak at diagnosis, GALIG gene expression also increases in BM and blood after chemotherapy treatment. These observations are reinforced by in vitro studies which indicate that GALIG expression increases early during polymorphonuclear and macrophages differentiations, before the onset of terminal maturation features. Cell survival during differentiation could be ensured by the increasing expression of the MCL1 which could counteract the apoptotic function of GALIG. In the blood of treated HIV-infected patients, without viral load, the transcription rate of GALIG is higher when compared to uninfected donors. This suggests a possible dysfunction of the immune system. In addition, several autophagy genes are dysregulated which could lead to the inhibition of the basal level of autophagy in these patients, which in turn could be a cause of the premature aging of blood cells and linked to the chronic inflammation reported for efficient treated HIV patients. In conclusion, these results encourage us to pursue studies deciphering the mechanisms of regulation of the GALIG gene expression and the mechanisms of action of the Galigins.
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Amandine Serrano. Expression de GALIG, gène inducteur de la mort cellulaire, dans des cellules normales et pathologiques. Sciences agricoles. Université d'Orléans, 2017. Français. ⟨NNT : 2017ORLE2019⟩. ⟨tel-01713116⟩

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