Fiche publication
Date publication
août 2021
Journal
Haematologica
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MARCAIS Ambroise
Tous les auteurs :
Forlani G, Shallak M, Tedeschi A, Cavallari I, Marçais A, Hermine O, Accolla RS
Lien Pubmed
Résumé
Adult T-cell leukemia-lymphoma (ATL), is a highly malignant T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1), characterized by a poor prognosis. Two viral proteins, Tax-1 and HBZ play important roles in the pathogenesis of ATL. While Tax-1 can be found in both cytoplasm and nucleus of HTLV-1 infected patients, HBZ is exclusively localized in the cytoplasm of HTLV-1 asymptomatic carriers and patients with chronic neurologic disease HAM/TSP, and only in the nucleus of ATL cell lines, suggesting that the nuclear localization of HBZ can be a hallmark of neoplastic transformation. To clarify this crucial point, here we investigated in detail the pattern of HBZ expression in ATL patients. We made use of our monoclonal antibody 4D4-F3, that at present is a uniquely reported reagent, among the few described, able to detect endogenous HBZ by immunofluorescence and confocal microscopy in cells from asymptomatic carriers, HAM/TSP and ATL patients. We found that HBZ localizes both in the cytoplasm and in the nucleus of cells of ATL patients irrespective of their clinical status, with a strong preference for the cytoplasmic localization. Also Tax-1 localized in both compartments. As HBZ is exclusively localized in the cytoplasm in asymptomatic carriers and in non-neoplastic pathologies, this finding shows that neoplastic transformation consequent to HTLV-1 infection is accompanied and associated with the capacity of HBZ to translocate to the nucleus, which suggests a role of cytoplasmic-to-nuclear translocation in HTLV-1-mediated oncogenesis.
Mots clés
Basic-Leucine Zipper Transcription Factors, genetics, Cytoplasm, Gene Products, tax, genetics, Human T-lymphotropic virus 1, Humans, Leukemia-Lymphoma, Adult T-Cell, genetics, Retroviridae Proteins, genetics, Viral Proteins
Référence
Haematologica. 2021 08 1;106(8):2076-2085
