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; Laydon, Daniel J.; Bain, Barbara J.; Fields, Paul; Taylor, Graham P.

doi:10.3324/haematol.2012.069476

Cited by 21 publications

(18 citation statements)

References 12 publications

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“…While Vakili et al . observed no significant association between PVL in HAM/TSP patients and healthy carriers with age and gender, it has been reported that for both HTLV-1 and 2 infections, women have lower PVL levels than men, consistent with our results [ 38 , 39 , 40 ]. In contrast, Hisada et al .…”

Section: Discussionsupporting

confidence: 92%

Low Proviral Load is Associated with Indeterminate Western Blot Patterns in Human T-Cell Lymphotropic Virus Type 1 Infected Individuals: Could Punctual Mutations be Related?

Cánepa

Salido

Ruggieri

et al. 2015

Viruses

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Background: indeterminate Western blot (WB) patterns are a major concern for diagnosis of human T-cell lymphotropic virus type 1 (HTLV-1) infection, even in non-endemic areas. Objectives: (a) to define the prevalence of indeterminate WB among different populations from Argentina; (b) to evaluate if low proviral load (PVL) is associated with indeterminate WB profiles; and (c) to describe mutations in LTR and tax sequence of these cases. Results: Among 2031 samples, 294 were reactive by screening. Of them, 48 (16.3%) were WB indeterminate and of those 15 (31.3%) were PCR+. Quantitative real-time PCR (qPCR) was performed to 52 HTLV-1+ samples, classified as Group 1 (G1): 25 WB+ samples from individuals with pathologies; Group 2 (G2): 18 WB+ samples from asymptomatic carriers (AC); and Group 3 (G3): 9 seroindeterminate samples from AC. Median PVL was 4.78, 2.38, and 0.15 HTLV-1 copies/100 PBMCs, respectively; a significant difference (p=0.003) was observed. Age and sex were associated with PVL in G1 and G2, respectively. Mutations in the distal and central regions of Tax Responsive Elements (TRE) 1 and 2 of G3 were observed, though not associated with PVL.The 8403A>G mutation of the distal region, previously related to high PVL, was absent in G3 but present in 50% of WB+ samples (p = 0.03). Conclusions: indeterminate WB results confirmed later as HTLV-1 positive may be associated with low PVL levels. Mutations in LTR and tax are described; their functional relevance remains to be determined.

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Section: Discussionsupporting

confidence: 92%

Low Proviral Load is Associated with Indeterminate Western Blot Patterns in Human T-Cell Lymphotropic Virus Type 1 Infected Individuals: Could Punctual Mutations be Related?

Cánepa

Salido

Ruggieri

et al. 2015

Viruses

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“…In a Japanese analysis, the only clinical correlates of the diagnosis of HAM/TSP were detection of brisk patellar tendon reflexes, which might reflect subclinical disease, and the presence of 'flower cells' 113 (HTLV-1-infected lymphocytes with a characteristic multilobular nucleus, Figure 6). Atypical lymphocytes with an abnormal nuclear morphology can be observed in people with any clinical manifestation of HTLV-1 infection; their presence is associated with inflammation rather than with a higher risk of ATL 114 .…”

Section: [H1] Diagnosis Screening and Prevention [H2] Use Of Risk Famentioning

confidence: 99%

“…The prevalence of subclinical signs or mild symptoms of HAM/TSP varies between populations. Family history frequently reveals a possible HTLV-1associated disease in a sibling or older relative, although often without a clear diagnosis.Carriers with a high HTLV-1 proviral load as well as patients with HAM/TSP are at greater risk of ATL114 .…”

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confidence: 99%

HTLV-1-associated myelopathy/tropical spastic paraparesis

Bangham

Araújo

Yamano

et al. 2015

Nat Rev Dis Primers

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Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the CNS that causes weakness or paralysis of the legs, lower back pain and urinary symptoms. HAM/TSP was first described in Jamaica in the nineteenth century, but the aetiology of the condition, infection with the retrovirus HTLV-1, was only identified in the 1980s. HAM/TSP causes chronic disability and, accordingly, imposes a substantial health burden in areas where HTLV-1 infection is endemic. Since the discovery of the cause of HAM/TSP, considerable advances have been made in the understanding of the virology, immunology, cell biology and pathology of HTLV-1 infection and its associated diseases. However, progress has been limited by the lack of accurate animal models of the disease. Moreover, the treatment of HAM/TSP remains highly unsatisfactory: antiretroviral drugs have little impact on the infection and, although potential disease-modifying therapies are widely used, their value is unproved. At present, clinical management is focused on symptomatic treatment and counselling. Here, we summarize current knowledge on the epidemiology, pathogenesis and treatment of HAM/TSP and identify areas in which further research is needed. For an illustrated summary of this Primer, visit: http://go.nature.com/tjZCFM.

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“…The development of ATL occurs almost exclusively in patients with a high HTLV‐1 proviral load (PVL) . Indeed in the United Kingdom cohort, incident ATL occurred only among patients with PVL >10% (37% of all patients) with a lifetime risk of 13.3 per 1000 patient‐years . These high PVL patients are thus considered high risk and there is a need for better risk stratification and prevention in this group.…”

Section: Introductionmentioning

confidence: 99%

Risk stratification of adult T‐cell leukemia/lymphoma using immunophenotyping

et al. 2016

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Adult T‐cell leukemia/lymphoma (ATL), a human T‐lymphotropic virus type 1 (HTLV‐1)‐associated disease, has a highly variable clinical course and four subtypes with therapeutic and prognostic implications. However, there are overlapping features between ATL subtypes and between ATL and nonmalignant (non‐ATL) HTLV‐1 infection complicating diagnosis and prognostication. To further refine the diagnosis and prognosis of ATL, we characterized the immunophenotype of HTLV‐1‐infected cells in ATL and non‐ATL. A retrospective study of peripheral blood samples from 10 HTLV‐1‐uninfected subjects (UI), 54 HTLV‐1‐infected patients with non‐ATL, and 22 with ATL was performed using flow cytometry. All patients with ATL had CD4+ CCR4+ CD26− immunophenotype and the frequency of CD4+ CCR4+ CD26− T cells correlated highly significantly with the proviral load in non‐ATL suggesting CD4+ CCR4+ CD26− as a marker of HTLV‐1‐infected cells. Further immunophenotyping of CD4+ CCR4+ CD26− cells revealed that 95% patients with ATL had a CD7− (≤30% CD7+ cells), whereas 95% HTLV+ non‐ATL had CD7+ (>30% CD7+ cells) immunophenotype. All patients with aggressive ATL had a CCR7+ (≥30%), whereas 92% with indolent ATL and 100% non‐ATL had a CCR7− (<30%) immunophenotype. Patients with nonprogressing indolent ATL were CD127+ but those with progressive lymphocytosis requiring systemic therapy had a CD127− (≤30%) immunophenotype. In summary, HTLV‐1‐infected cells have a CD4+ CCR4+ CD26− immunophenotype. Within this population, CD7− phenotype suggests a diagnosis of ATL, CCR7+ phenotype identifies aggressive ATL, while CCR7− CD127− phenotype identifies progressive indolent ATL.

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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

Cited by 21 publications

References 12 publications

Low Proviral Load is Associated with Indeterminate Western Blot Patterns in Human T-Cell Lymphotropic Virus Type 1 Infected Individuals: Could Punctual Mutations be Related?

Low Proviral Load is Associated with Indeterminate Western Blot Patterns in Human T-Cell Lymphotropic Virus Type 1 Infected Individuals: Could Punctual Mutations be Related?

HTLV-1-associated myelopathy/tropical spastic paraparesis

Risk stratification of adult T‐cell leukemia/lymphoma using immunophenotyping

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