2025 GIGA Annual Report | 17 Grégory Ehx (WELRI Investigator) and his team at the Laboratory of Hematology, in collaboration with Canadian researchers, have uncovered a key limitation of azacitidine (AZA), a firstline treatment for elderly acute myeloid leukemia (AML) patients. AZA is known to reactivate silenced genes, including endogenous retroelements (EREs), ancient viral sequences in our DNA. While ERE activation triggers antiviral immune responses that hinder leukemia progression, the team discovered that AZA simultaneously induces autophagy, a cellular recycling process that degrades EREs before they can be presented to the immune system. By inhibiting autophagy, they restored the ability of leukemia cells to present ERE-derived peptides, enhancing immune recognition. Moreover, AML patients with high ERE expression but low autophagy showed stronger T-cell responses. These findings, published in Leukemia, suggest that combining AZA with autophagy inhibitors—many of which are already clinically approved—could improve AML treatment outcomes. AUTOPHAGY DEGRADES IMMUNOGENIC ENDOGENOUS RETROELEMENTS INDUCED BY 5-AZACYTIDINE IN ACUTE MYELOID LEUKEMIA Noronha N, Durette C, Cahuzac M, E Silva B, Courtois J, Humeau J, Sauvat A, Hardy MP, Vincent K, Laverdure JP, Lanoix J, Baron F, Thibault P, Perreault C, Ehx G. Leukemia. 2024 May;38(5):1019-1031. doi: 10.1038/s41375-024-02250-6. p LINKS | News GIGA | Publication on ORBI | Grégory Ehx
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