Journal
CANCER LETTERS
Volume 389, Issue -, Pages 78-85Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.12.022
Keywords
STLV-1; Retrovirus; Leukemia/Lymphoma; Therapy; Clonality; LM-PCR
Categories
Funding
- ENS Lyon
- Contrat Hospitalier de recherche translationnelle (AP-HP Paris)
- Fondation ARC pour la Recherche sur le Cancer
- INSERM
- ARC
- La Ligue Contre le Cancer programme Equipe Labellisee
- Ecofect Labex
- grant of la ligue contre le cancer
- Institut National du cancer
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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(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 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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