title: Whole body clonality analysis in an aggressive STLV-1 associated leukemia (ATLL) reveals an unexpected clonal complexity.
abstract: HTLV-1 causes Adult T cell Leukemia/Lymphoma (ATLL) in humans. We describe an ATL-like disease in a 9 year-old female baboon naturally infected with STLV-1 (the simian counterpart of HTLV-1), with a lymphocyte count over 1010/L, lymphocytes with abnormal nuclear morphology, and pulmonary and skin lesions. The animal was treated with a combination of AZT and alpha interferon. Proviral load (PVL) was measured every week. Because the disease continued to progress, the animal was euthanized. Abnormal infiltrates of CD3+CD25+lymphocytes and Tax-positive cells were found by histological analyses in both lymphoid and non-lymphoid organs. PVL was measured and clonal diversity was assessed by LM-PCR (Ligation-Mediated Polymerase Chain Reaction) and high throughput sequencing, in blood during treatment and in 14 different organs. The highest PVL was found in lymph nodes, spleen and lungs. One major clone and a number of intermediate abundance clones were present in blood throughout the course of treatment, and in organs. These results represent the first multi-organ clonality study in ATLL. We demonstrate a previously undescribed clonal complexity in ATLL. Our data reinforce the usefulness of natural STLV-1 infection as a model of ATLL.
authors.affiliation: International Center for Research in Infectiology, Retroviral Oncogenesis Laboratory, INSERM U1111 - Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, F-69007, Lyon, France; Equipe labellisée "Ligue Nationale Contre le Cancer", France; Section of Virology, Department of Medicine, Imperial College London, London, W2 1PG, UK. Electronic address: j.turpin@imperial.ac.uk.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Turpin
authors.affiliation: International Center for Research in Infectiology, Retroviral Oncogenesis Laboratory, INSERM U1111 - Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, F-69007, Lyon, France; Equipe labellisée "Ligue Nationale Contre le Cancer", France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Alais
authors.affiliation: Equipe labellisée "Ligue Nationale Contre le Cancer", France; Service d'hématologie adulte, centre de référence des mastocytoses, hôpital Necker Enfant Malade, assistance publique Hôpitaux de Paris, Université Paris Descartes, 75015, Paris, France; INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Imagine Institute Hôpital Necker, Paris, France.
authors.forename: Ambroise
authors.initials: A
authors.lastname: Marçais
authors.affiliation: Equipe labellisée "Ligue Nationale Contre le Cancer", France; INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Imagine Institute Hôpital Necker, Paris, France; Service d'Anatomie et Cytologie Pathologiques, Faculté de Médecine et AP-HP, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris Sorbonne Cité, Paris Cedex, 15, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, W2 1PG, UK.
authors.forename: Anat
authors.initials: A
authors.lastname: Melamed
authors.affiliation: Anipath, UFR Médecine Lyon-RTH Laennec, Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gadot
authors.affiliation: Department of Immunology, Graduate School of Medicine University of the Ryukyus Uehara 207, Nishihara-cho, Okinawa, 903-0125, Japan.
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Equipe labellisée "Ligue Nationale Contre le Cancer", France; Service d'hématologie adulte, centre de référence des mastocytoses, hôpital Necker Enfant Malade, assistance publique Hôpitaux de Paris, Université Paris Descartes, 75015, Paris, France; INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Imagine Institute Hôpital Necker, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Station de Primatologie-UPS846-CNRS, Rousset sur Arc, 13790, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Melot
authors.affiliation: Station de Primatologie-UPS846-CNRS, Rousset sur Arc, 13790, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Lacoste
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, W2 1PG, UK.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Bangham
authors.affiliation: International Center for Research in Infectiology, Retroviral Oncogenesis Laboratory, INSERM U1111 - Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, F-69007, Lyon, France; Equipe labellisée "Ligue Nationale Contre le Cancer", France. Electronic address: renaud.mahieux@ens-lyon.fr.
authors.forename: Renaud
authors.initials: R
authors.lastname: Mahieux
mesh_terms: D000818:Animals; D006800:Deltaretrovirus Infections / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D016898:Interferon-alpha / Q000494:pharmacology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008992:Monkey Diseases / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D010215:Papio; D015303:Simian T-lymphotropic virus 1; D019562:Viral Load; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D016898:Interferon-alpha; D015215:Zidovudine
keywords: Clonality; LM-PCR; Leukemia/Lymphoma; Retrovirus; STLV-1; Therapy