Whole body clonality analysis in an aggressive STLV-1 associated leukemia (ATLL) reveals an unexpected clonal complexity
File(s)
Accepted version
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2016-12-26
Date Acceptance
2016-12-19
Citation
CANCER LETTERS, 2016, 389, pp.78-85
ISSN
0304-3835
Publisher
ELSEVIER
Start Page
78
End Page
85
Journal / Book Title
CANCER LETTERS
Volume
389
Copyright Statement
© 2016 Elsevier Ireland Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000395846100009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
STLV-1
Retrovirus
Leukemia/Lymphoma
Therapy
Clonality
LM-PCR
T-CELL LEUKEMIA
VIRUS TYPE-I
SPONTANEOUS MALIGNANT-LYMPHOMA
BLOOD MONONUCLEAR-CELLS
HTLV-1 INFECTION
NONHUMAN-PRIMATES
CENTRAL-AFRICA
NATURAL INFECTION
PROVIRAL LOAD
TYPE-1
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
Publication Status
Published