title: Tax unleashed: fulminant Tax-positive Adult T-cell Leukemia/Lymphoma after failed allogeneic stem cell transplantation.
abstract: The human retrovirus HTLV-1 causes Adult T-cell Leukemia/Lymphoma (ATLL), a malignant lymphoproliferative disease of CD4+ T cells of dismal prognosis, in 3-5% of the 20 million infected individuals (Proietti et al.(1) and Bazarbachi et al.(2)). Infection with HTLV-1 represents a prototypical model of virus-mediated oncogenesis by virtue of the viral transactivator Tax, a potent oncogenic protein that exerts pleiotropic effects through its ability to deregulate the transcription of various cellular genes and signal transduction pathways and inhibit DNA repair enzymes, which are critical for T-cell homeostasis and genetic stability (Matsuoka and Jeang(3)) (et Boxus Retrovirology 2009). However, the oncogenic potential of Tax remains a conundrum. Tax protein expression is undetectable using conventional methods in freshly harvested ATLL cells and in non-malignant infected CD4+ T cells (Furukawa et al.(4)) but is up regulated after only a few hours of culture in vitro (Hanon et al.(5)). These observations strongly suggest that a host-derived mechanism is able to either actively repress the transcription of viral proteins in vivo or refrain the emergence of Tax-expressing cells, which would have a growth advantage. We report herein a unique case of CD4+ T-cell leukemia highly expressing Tax following rejection of an allogenic peripheral blood stem cell graft for an HTLV-1 associated lymphoma.
authors.affiliation: Service d'Hématologie Adultes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Ghez
authors.forename: Amédée
authors.initials: A
authors.lastname: Renand
authors.forename: Yves
authors.initials: Y
authors.lastname: Lepelletier
authors.forename: David
authors.initials: D
authors.lastname: Sibon
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Rubio
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.forename: Agnès
authors.initials: A
authors.lastname: Buzyn
authors.forename: Kheira
authors.initials: K
authors.lastname: Beljord
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Bruno
authors.initials: B
authors.lastname: Varet
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016356:Gene Products, tax / Q000276:immunology / Q000378:metabolism*; D015490:HTLV-I Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male
chemical_list: D016356:Gene Products, tax