The Oncoprotein Fra-2 Drives the Activation of Human Endogenous Retrovirus Env Expression in Adult T-Cell Leukemia/Lymphoma (ATLL) Patients.
Julie Tram, Laetitia Marty, C��lima Mourouvin, Magali Abrantes, Ilham Jaafari, Raymond C��saire, Philippe H��lias, Benoit Barbeau, Jean-Michel Mesnard, V��ronique Baccini, Laurent Chaloin, Jean-Marie Jr Peloponese
Author Information
Julie Tram: Universit�� Montpellier (UM), 34000 Montpellier, France. ORCID
Laetitia Marty: Universit�� Montpellier (UM), 34000 Montpellier, France. ORCID
C��lima Mourouvin: Universit�� Montpellier (UM), 34000 Montpellier, France.
Magali Abrantes: Universit�� Montpellier (UM), 34000 Montpellier, France.
Ilham Jaafari: Universit�� Montpellier (UM), 34000 Montpellier, France.
Raymond C��saire: Centre Hospitalier Universitaire de Martinique, 97261 Fort de France, France.
Philippe H��lias: D��partement de Radioth��rapie-Oncologie-H��matologie, Centre Hospitalier Universitaire de la Guadeloupe, 97110 Pointe �� Pitre, France.
Benoit Barbeau: D��partement des Sciences Biologiques, Universit�� du Qu��bec �� Montr��al, SB-R860, Montr��al, QC H2X 1Y4, Canada. ORCID
Jean-Michel Mesnard: Universit�� Montpellier (UM), 34000 Montpellier, France. ORCID
V��ronique Baccini: Laboratoire d'H��matologie CHU de la Guadeloupe, 97110 Pointe �� Pitre Guadeloupe, France. ORCID
Laurent Chaloin: Universit�� Montpellier (UM), 34000 Montpellier, France. ORCID
Jean-Marie Jr Peloponese: Universit�� Montpellier (UM), 34000 Montpellier, France. ORCID
Human endogenous retroviruses (HERVs) are retroviral sequences integrated into 8% of the human genome resulting from ancient exogenous retroviral infections. Unlike endogenous retroviruses of other mammalian species, HERVs are mostly replication and retro-transposition defective, and their transcription is strictly regulated by epigenetic mechanisms in normal cells. A significant addition to the growing body of research reveals that HERVs' aberrant activation is often associated with offsetting diseases like autoimmunity, neurodegenerative diseases, cancers, and chemoresistance. Adult T-cell leukemia/lymphoma (ATLL) is a very aggressive and chemoresistant leukemia caused by the human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATLL remains poor despite several new agents being approved in the last few years. In the present study, we compare the expression of HERV genes in CD8-depleted PBMCs from HTLV-1 asymptomatic carriers and patients with acute ATLL. Herein, we show that HERVs are highly upregulated in acute ATLL. Our results further demonstrate that the oncoprotein Fra-2 binds the LTR region and activates the transcription of several HERV families, including HERV-H and HERV-K families. This raises the exciting possibility that upregulated HERV expression could be a key factor in ATLL development and the observed chemoresistance, potentially leading to new therapeutic strategies and significantly impacting the field of oncology and virology.
