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Pre-morbid human T-lymphotropic virus type I proviral load, rather than percentage of abnormal lymphocytes, is associated with an increased risk of aggressive adult T-cell leukemia/lymphoma.

ABSTRACT: Out of 153 newly referred human T-lymphotropic virus type I infected patients, 42 (27%) had 5% or more abnormal lymphocytes, consistent with the diagnosis of smoldering adult T-cell leukemia/lymphoma. The abnormal lymphocyte percentage was higher in patients with human T-lymphotropic virus type I associated inflammatory disease compared with asymptomatic carriers (P=0.006). Over 4.5 years median follow up, 4 patients, all with 10 or more human T-lymphotropic virus type I DNA copies/100 peripheral blood mononuclear cells at presentation, but only one with 5% or more abnormal lymphocytes at presentation, developed adult T-cell leukemia/lymphoma. Thus, high pre-morbid human T-lymphotropic virus type I proviral load, rather than fulfilment of the classification criteria for smoldering adult T-cell leukemia/lymphoma, was associated with an increased risk of developing aggressive adult T-cell leukemia/lymphoma.

SUBMITTER: Hodson A

PROVIDER: S-EPMC3659941 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Pre-morbid human T-lymphotropic virus type I proviral load, rather than percentage of abnormal lymphocytes, is associated with an increased risk of aggressive adult T-cell leukemia/lymphoma.

Hodson Andrew A Laydon Daniel J DJ Bain Barbara J BJ Fields Paul A PA Taylor Graham P GP

Haematologica 20120808 3

Out of 153 newly referred human T-lymphotropic virus type I infected patients, 42 (27%) had 5% or more abnormal lymphocytes, consistent with the diagnosis of smoldering adult T-cell leukemia/lymphoma. The abnormal lymphocyte percentage was higher in patients with human T-lymphotropic virus type I associated inflammatory disease compared with asymptomatic carriers (P=0.006). Over 4.5 years median follow up, 4 patients, all with 10 or more human T-lymphotropic virus type I DNA copies/100 periphera ...[more]

PMID: 22875625

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Project description:BACKGROUND: In vitro studies have demonstrated that deletions and point mutations introduced into each 21 bp imperfect repeat of Tax-responsive element (TRE) of the genuine human T-cell leukemia virus type I (HTLV-1) viral promoter abolishes Tax induction. Given these data, we hypothesized that similar mutations may affect the proliferation of HTLV-1-infected cells and alter the proviral load (PvL). To test this hypothesis, we conducted a cross-sectional genetic analysis to compare the near-complete LTR nucleotide sequences that cover the TRE1 region in a sample of HTLV-1 asymptomatic carriers with different PvL burden. METHODS: A total of 94 asymptomatic HTLV-1 carriers with both sequence from the 5' long terminal repeat (LTR) and a PvL for Tax DNA measured using a sensitive SYBR Green real-time PCR were studied. The 94 subjects were divided into three groups based on PvL measurement: 31 low, 29 intermediate, and 34 high. In addition, each group was compared based on sex, age, and viral genotypes. In another analysis, the median PvLs between individuals infected with mutant and wild-type viruses were compared. RESULTS: Using a categorical analysis, a G232A substitution, located in domain A of the TRE-1 motif, was detected in 38.7% (12/31), 27.5% (8/29), and 61.8% (21/34) of subjects with low, intermediate, or high PvLs, respectively. A significant difference in the detection of this mutation was found between subjects with a high or low PvL and between those with a high or intermediate PvL (both p < 0.05), but not between subjects with a low or intermediate PvL (p > 0.05). This result was confirmed by a non-parametric analysis that showed strong evidence for higher PvLs among HTLV-1 positive individuals with the G232A mutation than those without this mutation (p < 0.03). No significant difference was found between the groups in relation to age, sex or viral subtypes (p > 0. 05). CONCLUSIONS: The data described here show that changes in domain A of the HTLV-1 TRE-1 motif resulting in the G232A mutation may increase HTLV-1 replication in a majority of infected subjects.

Dataset Information

Pre-morbid human T-lymphotropic virus type I proviral load, rather than percentage of abnormal lymphocytes, is associated with an increased risk of aggressive adult T-cell leukemia/lymphoma.

Publications

Pre-morbid human T-lymphotropic virus type I proviral load, rather than percentage of abnormal lymphocytes, is associated with an increased risk of aggressive adult T-cell leukemia/lymphoma.

Similar Datasets

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