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The expression of HERVs and their immune impact have not been extensively studied in Acute Myeloid Leukemia (AML). In this study, we used a reference of 14\u2009968 HERV functional units to provide a thorough analysis of HERV expression in normal and AML bone marrow cells. We show that the HERV retrotranscriptome accurately characterizes normal and leukemic cell subpopulations, including leukemia stem cells, in line with different epigenetic profiles. We then show that HERV expression delineates AML subtypes with different prognoses. We finally propose a method to select and prioritize CD8<jats:sup>+<\/jats:sup> T cell epitopes derived from AML\u2010specific HERVs and we show that lymphocytes infiltrating patient bone marrow at diagnosis contain naturally occurring CD8<jats:sup>+<\/jats:sup> T cells against these HERV epitopes. We also provide in vitro data supporting the functionality of HERV\u2010specific CD8<jats:sup>+<\/jats:sup> T\u2010cells against AML cells. 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