Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult T cell leukaemia-lymphoma (ATL) was first discovered and reported in Japan, where it has a high incidence in the south-west region. The first human retrovirus HTLV-I (human T-cell lymphotropic virus type I) is considered to be related to its aetiology. In ATL endemic areas, HTLV-I carriers form a fairly high percentage of the population, even among healthy individuals. ATL shows diverse clinical features. It can be divided into four subtypes: acute, chronic, smouldering and lymphoma type. ATL cells originate from the CD4-positive subset of peripheral T cells; they show a characteristic notch in the nucleus and a tendency to lobulation. ATL resists chemotherapy, and patients with acute and lymphoma types have a fairly poor prognosis. A definite diagnosis of ATL is made by documenting the presence of HTLV-I proviral DNA in the DNA of tumour cells. HTLV-I infection is caused by transmission of live lymphocytes via three routes (from mother to child, from males to females, and by transfusion). Familial occurrence of ATL is frequently seen. HTLV-I infection is seen in other countries, but its incidence is highest in Japan. Infection with HTLV-I is a direct cause of ATL. Furthermore, infection with this virus can indirectly cause many other diseases via the induction of immunodeficiency, such as chronic lung disease, opportunistic lung infection, cancer of other organs, monoclonal gammopathy, chronic renal failure, strongyloidiasis, non-specific dermatomycosis, HTLV-I-associated lymphadenitis, HTLV-I uveitis and HTLV-I-associated myelopathy-tropical spastic paraparesis (HAM/TSP).
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PMID:Adult T cell leukaemia-lymphoma. 803 96

Two distinct diseases, adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), develop in a minor population of HTLV-1 carriers. We examined the relationship between the viral genome dose in the peripheral-blood mononuclear cells and the serological response in HTLV-1 carriers and patients with HAM/TSP. The antibody titer to HTLV-1 gag and env proteins, as well as the frequency of an antibody response to viral protein p40tax and the titer, increased with increasing viral genome dose. However, the number of abnormal lymphocytes was not directly related to the host viral load. Patients with HAM/TSP generally showed a higher genome dose than healthy carriers and also had higher antibody titers than healthy carriers with the same HTLV-1 load, supporting the existence of an augmented immune response in these patients. These findings suggest that the antibody titer to HTLV-1 genome products, and not the number of abnormal lymphocytes, intimately reflects the approximate viral load in HTLV-1-infected individuals.
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PMID:Relationship between the anti-HTLV-1 antibody level, the number of abnormal lymphocytes and the viral-genome dose in HTLV-1-infected individuals. 809 12

The human T-cell leukemia type I (HTLV-I) virus is associated with two different diseases, adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). We have compared the viral envelopes originating from TSP/HAM and ATL patients, using the capacity of infected cells to form syncytia with receptor-expressing cells. We show that like the ATL cell lines, the TSP/HAM ones can form syncytia with a large panel of human target cells, including a variety of hematopoietic cell lines, as well as cell lines of neuroectodermal origin. None of the target cell lines tested was able to discriminate between TSP/HAM- and ATL-infected cell lines. When infected cells of TSP/HAM origin are cocultivated with cells of ATL origins, syncytia are never observed. This interference phenomenon suggests that the viruses expressed by the different cell lines utilize the same receptor.
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PMID:Functional comparison between HTLV-I envelopes originating from TSP/HAM or ATL cell lines. 813 44

Regulatory protein Tax of human T cell leukemia virus type 1 (HTLV-1) positively regulates the transcription of its own genome and specific cellular genes, and contributes to the pathogenicity in ATL, HAM/TSP and other associated diseases. The one mechanism of the transcriptional activation includes binding of Tax protein in nucleus to enhancer binding proteins of CREB, CREM, NF-kappa B p50, NF-kappa B p105 and SRF which bind to enhancer DNA. The other includes Tax-binding to NF-kappa B proteins in the cytoplasm resulting in nuclear translocation of active transcription factors. The interaction of Tax with cellular transcription factors thus ultimately results in cellular proliferation, immortalization and transformation leading to specific diseases.
Leukemia 1994 Apr
PMID:Mechanism of transcriptional activation of viral and cellular genes by oncogenic protein of HTLV-1. 815 4

The cytotoxic T cell response of peripheral blood mononuclear cells (PBMC) to in vitro stimulation with human T cell leukemia virus type I (HTLV-I) was compared among HTLV-I-infected individuals with various clinical conditions. Induction of HTLV-I-specific cytotoxic T lymphocytes (CTL) was observed in 57% of asymptomatic HTLV-I carriers, 86% of patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) or other HTLV-I-related inflammatory diseases, and 18% of adult T cell leukemia (ATL) patients. HTLV-I p40tax, one of the major CTL target antigens, has an epitope strongly associated with HLA-A2. HTLV-I p40tax-specific CTL were frequently induced from HLA-A2-positive donors with HTLV-I-related inflammatory diseases regardless of neurological symptoms, but not from all the HLA-A2-positive HTLV-I-infected individuals tested. Leukemic cells of an ATL patient with HLA-A2, whose PBMC did not show an HTLV-I-specific CTL response, could be lyzed by p40tax-specific CTL derived from an HAM/TSP patient. This indicates that i) the presence of a certain HLA presenting CTL epitopes is not the sole determinant of the individual CTL response to HTLV-I, ii) HTLV-I-specific CTL act as potential effectors of anti-tumor surveillance in vivo. The role of HTLV-I-specific CTL, however, may be limited by another in vivo mechanism suppressing the expression of HTLV-I antigens. This suppression, presumably mediated by a plasma factor and commonly observed in HTLV-I-infected individuals, could be one reason for the persistence of HTLV-I-infection.
Leukemia 1994 Apr
PMID:Cytotoxic T cell response and expression of the target antigen in HTLV-I infection. 815 5

In addition to adult T-cell leukemia (ATL) and chronic myelopathy (HAM/TSP), our current study indicates that human T lymphotropic virus type I (HTLV-I) is a causative agent for a specific type of uveitis with unknown etiology (idiopathic uveitis). The present paper describes the seroepidemiological, clinical, and molecular biological evidences that indicate uveitis seen in HTLV-I asymptomatic carriers (HTLV-I uveitis) is a distinct clinical entity. In an HTLV-I endemic area in Japan, the seroprevalence of HTLV-I in idiopathic uveitis was 38%, while those in uveitis with defined etiology and in non-uveitic ocular diseases were 10% and 19%, respectively. Strikingly, the HTLV-I seroprevalence in younger aged patients (20-49 years) with idiopathic uveitis was 49%, while only 8% in the control group (P < 0.001). A very similar observation was recorded even in HTLV-I less endemic area, suggesting that HTLV-I infection plays a role as a risk factor for idiopathic uveitis. Clinical analysis revealed that an intermediate uveitis characterized by moderate opacities in the vitreous body and retinal vasculitis was seen in the majority the patients. The proviral DNA of HTLV-I was detected from inflammatory cells in the eye of all tested patients using PCR technique. These data thus indicate that HTLV-I is closely related to a certain type of uveitis and the uveitis (HTLV-I uveitis) is a distinct clinical entity.
Leukemia 1994 Apr
PMID:Human T-lymphotropic virus type I uveitis. 815 12

Human T cell lymphotropic virus type I (HTLV-I) infection in India has been found to be associated with adult T cell leukaemia/lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) among life-long residents of southern India. To examine the heterogeneity of HTLV-I strains from southern India and to determine their relationship with the sequence variants of HTLV-I from Melanesia, 1149 nucleotides spanning selected regions of the HTLV-I gag, pol, env and pX genes were amplified and directly sequenced from DNA extracted from whole blood blotted onto filter paper and from peripheral blood mononuclear cells, obtained from one patient with HAM/TSP, two with ATLL and eight asymptomatic carriers from Andhra Pradesh, Kerala and Tamil Nadu. Sequence alignments and comparisons indicated that the 11 HTLV-I strains from southern India were 99.2% to 100% identical among themselves and 98.7% to 100% identical to the Japanese prototype HTLV-I ATK. The majority of base substitutions were transitions and silent. No frameshifts, insertions, deletions or possibly disease-specific base changes were found in the regions sequenced. The observed clustering of the Indian HTLV-I strains with those from Japan, as determined by the maximum parsimony method, suggested a common source of HTLV-I infection with subsequent parallel evolution. Amplification of DNA from blood specimens collected on filter paper may be useful for the study of other blood-borne pathogens.
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PMID:Sequence analysis of human T cell lymphotropic virus type I strains from southern India: gene amplification and direct sequencing from whole blood blotted onto filter paper. 827 90

Human T-cell leukemia virus type I (HTLV-I) is recognized as the etiologic agent of adult T-cell leukemia (ATL), a disease endemic in certain regions of southeastern Japan, Africa, and the Caribbean basin. Although HTLV-I can immortalize T lymphocytes in culture, factors leading to tumor progression after HTLV-I infection remain elusive. Previous attempts to propagate the ATL tumor cells in animals have been unsuccessful. Severe combined immunodeficient (SCID) mice have previously been used to support the survival of human lymphoid cell populations when inoculated with human peripheral blood lymphocytes (PBL). SCID mice were injected intraperitoneally with PBL from patients diagnosed with ATL, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or from asymptomatic HTLV-I-seropositive patients. Many of these mice become persistently infected with HTLV-I. Furthermore, after human reconstitution was established in these mice, HTLV-I-infected cells displayed a proliferative advantage over uninfected human cells. Lymphoblastic lymphomas of human origin developed in animals injected with PBL from two ATL patients. The tumor cells represented outgrowth of the original ATL leukemic clone in that they had monoclonal or oligoclonal integrations of the HTLV-I provirus identical to the leukemic clone and predominantly expressed the cell surface markers, CD4 and CD25. In contrast, cell lines derived by HTLV immortalization of T cells in vitro did not persist or form tumors when inoculated into SCID mice, indicating differences between in vitro immortalized cells and ATL leukemic cells. This system represents the first small animal model to study HTLV-I tumorigenesis in vivo.
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PMID:Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice. 833 42

To assess the immunopathological significance of the increased replication of human T-cell leukemia virus type I (HTLV-I) in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) we investigated the dynamics of HTLV-I proviral DNA in peripheral blood mononuclear cells (PBMC) of HAM/TSP patients at different clinical stages. We compared the dynamics to those of asymptomatic HTLV-I carriers (AC). The estimation of the amount of HTLV-I proviral DNA was carried out by quantitative polymerase chain reaction of serially diluted DNA samples where it was feasible to titrate 0.04-80 copies per 100 PBMC. The proviral DNA quantified in six patients with HAM/TSP was 2-20 copies per 100 PBMC, while that in eight cases of AC was 0.04-8 copies per 100 PBMC. Thus, the amount of HTLV-I proviral DNA in HAM/TSP patients was 3-50 times as high as that of AC. When we followed up HAM/TSP patients for 1-3 years, the amount of HTLV-I proviral DNA fluctuated from 4 to 10-fold. These data suggest that the rate of HTLV-I replication increases in HAM/TSP and the amount of HTLV-I proviral DNA fluctuates in their clinical course. Fluctuation in the amount of HTLV-I proviral DNA may reflect dynamics of HTLV-I infected cell proliferation and immunological suppression in vivo in HAM/TSP patients.
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PMID:Fluctuation of HTLV-I proviral DNA in peripheral blood mononuclear cells of HTLV-I-associated myelopathy. 842

Human T-cell leukemia virus type I (HTLV-I) has been associated with adult T-cell leukemia/lymphoma and the chronic neurologic disorder tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). To study the genetic structure of the virus associated with TSP/HAM, we have obtained and sequenced a partial genomic clone from an HTLV-I-positive cell line established from cerebrospinal fluid (CSF) of a Jamaican patient with TSP/HAM. This clone consisted of a 4.3-kb viral sequence containing the 5' long terminal repeat (LTR), gag, and N-terminal portion of the pol gene, with an overall 1.3% sequence variation resulting from mostly nucleotide substitutions, as compared to the prototype HTLV-I ATK-1. The gag and pol regions showed only 1.4% and 1.2% nucleotide variations, respectively. However, the U3 region of the LTR showed the highest sequence variation (3.6%), where several changes appear to be common among certain TSP/HAM isolates. Several of these changes reside within the 21-bp boundaries and the Tax-responsive element. It would be important to determine if the observed changes are sufficient to cause neurologic disorders similar to the murine leukemia virus system or simply reflect the divergent pool of HTLV-I from different geographic locations. At this time, we cannot rule out the possibility that the observed changes have either direct or indirect significance for the HTLV-I pathogenesis in TSP/HAM.
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PMID:Nucleotide sequence analysis of HTLV-I isolated from cerebrospinal fluid of a patient with TSP/HAM: comparison to other HTLV-I isolates. 845 77


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