Turpin Jocelyn, Alais Sandrine, Marçais Ambroise, Bruneau Julie, Melamed Anat, Gadot Nicolas, Tanaka Yuetsu, Hermine Olivier, Melot Sandrine, Lacoste Romain, Bangham Charles R, Mahieux Renaud
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.
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.
Cancer Lett. 2017 Mar 28;389:78-85. doi: 10.1016/j.canlet.2016.12.022. Epub 2016 Dec 26.
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 10/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 CD3CD25 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.
人类嗜T淋巴细胞病毒1型（HTLV-1）可导致人类患成人T细胞白血病/淋巴瘤（ATLL）。我们描述了一只自然感染猴嗜T淋巴细胞病毒1型（STLV-1，HTLV-1的猴类对应病毒）的9岁雌性狒狒患有一种类似ATL的疾病，其淋巴细胞计数超过10/L，淋巴细胞核形态异常，并有肺部和皮肤病变。该动物接受了齐多夫定（AZT）和α干扰素联合治疗。每周测量前病毒载量（PVL）。由于疾病持续进展，该动物被实施安乐死。通过组织学分析在淋巴器官和非淋巴器官中均发现了CD3CD25淋巴细胞和Tax阳性细胞的异常浸润。在治疗期间对血液以及14个不同器官中的PVL进行了测量，并通过连接介导的聚合酶链反应（LM-PCR）和高通量测序评估了克隆多样性。在淋巴结、脾脏和肺中发现了最高的PVL。在整个治疗过程中，血液和器官中均存在一个主要克隆和一些中等丰度的克隆。这些结果代表了ATLL中首次多器官克隆性研究。我们证明了ATLL中一种此前未被描述的克隆复杂性。我们的数据强化了自然STLV-1感染作为ATLL模型的有用性。
