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At least 937 records · Page 52Linked to original sources
PubMed2002

Repression of IRF-4 target genes in human T cell leukemia virus-1 infection.

The human T cell leukemia/lymphotropic virus-1 (HTLV-I) is the etiologic agent of adult T cell leukemia (ATL), an aggressive and fatal leukemia of CD4+ T lymphocytes. Interferon regulatory factor-4 (IRF-4) was shown previously to be constitutively expressed in T cells infected with HTLV-1. In this study, we investigated the role of IRF-4 gene regulation in the context of HTLV-1 infection using gene array technology and IRF-4 expressing T cells. Many potential IRF-4 regulated genes were identified, the vast majority of which were repressed by IRF-4 expression. Cyclin B1, a G2-M checkpoint protein identified as an IRF-4 repressed gene in the array, was further characterized in the context of HTLV-1 infection. All HTLV-1 infected cell lines and ATL patient lymphocytes demonstrated a dramatic decrease in cyclin B1 levels; subsequent analysis of the cyclin B1 promoter identified two sites important in IRF-4 binding and repression of cyclin B1 expression. Furthermore, IRF-4-mediated repression of cyclin B1 led to a significant decrease in CDC2 kinase activity in HTLV-1 infected T cells. IRF-4 expression in HTLV-1 infected T cells also downregulated other genes implicated in the mitotic checkpoint as well as genes involved in actin cytoskeletal rearrangement, DNA repair, apoptosis, metastasis and immune recognition. Several of the identified genes are dysregulated in ATL and may provide important mechanistic information concerning pathways critical to the emergence of ATL.

Base Sequence↗
PubMed2005

Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response.

Human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL), a rapidly progressing, clonal malignancy of CD4+ T lymphocytes. Fewer than one in 20 infected individuals typically develop ATL and the onset of this cancer occurs after decades of relatively symptom-free infection. Leukemic cells from ATL patients display extensive and varied forms of chromosomal abnormalities and this genomic instability is thought to be a major contributor to the development of ATL. HTLV-I encodes a regulatory protein, Tax, which is necessary and sufficient to transform cells and is therefore considered to be the viral oncoprotein. Tax interacts with numerous cellular proteins to reprogram cellular processes including, but not limited to, transcription, cell cycle regulation, DNA repair, and apoptosis. This review presents an overview of the impact of HTLV-I infection in general, and Tax expression in particular, on cell cycle progression and the repair of DNA damage. The contribution of these activities to genome instability and cellular transformation will be discussed.

Cell Cycle↗
PubMed2003

Downregulation of Bcl-xL and activation of caspases during retinoic acid-induced apoptosis in an adult T-cell leukemia cell line.

INTRODUCTION: Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I). We previously reported that retinoic acid (RA) isomers, all-trans-RA (ATRA), 9-cis-RA and 13-cis-RA, induce growth arrest and apoptosis in ATL cell lines. In this study we investigate the mechanisms of apoptosis induced by RAs. MATERIALS AND METHODS: An ATL cell line, KK1, established from an ATL patient was cultured with or without RAs. DNA fragmentation was analyzed using propidium iodide for staining DNA on a FACS. The apoptosis-related proteins and their transcriptional levels were thereafter analyzed by Western blotting and reverse transcription polymerase chain reaction (RT-PCR). Caspase activity was determined by using specific fluorogenic substrates. RESULTS: Bcl-2 and Bcl-xL are constitutively expressed in KK1. Treatment with RAs caused the level of Bcl-x protein decreased, while the levels of Bcl-2 and Bcl-xS remained unchanged. The level of Bax tended to decrease. There was a reduction of mitochondrial membrane potential and activation of caspase-3 and -6 without any activation of caspase-1. Broad range caspase inhibitors, Z-Asp and Z-VAD, prevented DNA fragmentation. CONCLUSION: These results suggest that the RA-induced apoptotic signals were transduced via downregulation of Bcl-xL and the decrease in the mitochondrial membrane function leading to caspase-3 activation.

Adult↗
PubMed2004

Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma.

Human T-cell lymphotropic virus type 1 associated adult T-cell leukemia/lymphoma carries a very poor prognosis due to its intrinsic resistance to chemotherapy. Although zidovudine (AZT) and alpha-interferon (IFN) yield some responses and improve ATL prognosis, alternative therapies are needed. Arsenic trioxide (As) dramatically synergizes with IFN to induce growth arrest and apoptosis of ATL leukemia cells in vitro. These results prompted us to initiate a phase II trial of As/IFN combination in seven patients with relapsed/refractory ATL (four acute and three lymphoma). Four patients exhibited a clear initial response (one complete remission and three partial remissions). Yet, the treatment was discontinued after a median of 22 days because of toxicity (three patients) or subsequent progression (four patients). Six patients eventually died from progressive disease (five patients) or infection (one patient), but the remaining patient is still alive and disease free at 32 months. Pharmacokinetic studies showed that maximum arsenic blood levels (median 0.46 microM) were slowly achieved (8-15 days). In conclusion, arsenic/IFN treatment is feasible and exhibits an anti-leukemia effect in very poor prognosis ATL patients despite a significant toxicity. Future studies should assess the best timing for arsenic therapy: frontline with IFN/AZT or as maintenance after induction.

Adult↗
PubMed2001

Lymphoma-type adult T-cell leukaemia-lymphoma with a bulky cutaneous tumour showing multiple human T-lymphotropic virus-1 DNA integration.

Human T-lymphotropic virus-1 (HTLV-1) is considered to be the cause of adult T-cell leukaemia-lymphoma (ATL). Monoclonal integration of HTLV-1 proviral DNA, as is analysed by Southern blotting, has been demonstrated in ATL patients. Unusual integration patterns of HTLV-1 proviral DNA have occasionally been described, and it is suggested that the patterns have clinical implications for ATL pathophysiology. Multiple, complete and defective types of integration patterns, in that order, are apparently associated with prognoses from good to poor. We report a 73-year-old Japanese woman with lymphoma-type ATL and a bulky cutaneous tumour on the left thigh. Four bands of slightly differing intensity were seen after EcoRI digestion of skin and lymph node samples on Southern blot analysis of HTLV-1 proviral DNA. Analysis for T-cell receptor-beta gene revealed five novel bands after restriction enzyme digestion with HindIII, indicating that the patient has four separate tumour cell clones, each of which carries one copy of the provirus. She was treated with chemotherapy and radiation and remains under reasonable control despite some relapsing cutaneous nodules. The indolent course in this present case could be related to the multiple integration pattern of HTLV-1 proviral DNA detected.

Aged↗
PubMed1996

Adult T-cell leukaemia/lymphoma with multiple integrations of human T-cell lymphotropic virus type I proviral DNA: differing clinical features are linked to varied proviral integration.

Multiple integrations of human T-cell lymphotropic virus type I (HTLV-I) proviral DNA are occasionally found in tumor cells from patients with adult T-cell leukaemia/lymphoma (ATL). However, the clinical implications of multiple integrations of HTLV-I in ATL have not been well established. We studied 95 patients with ATL to elucidate the relationship between the multiple integrations of HTLV-I and the clinical characteristics. The proviral DNA of HTLV-I was examined by standard Southern blot analysis using the probe of an entire HTLV-I genome and the endonucleases with or without cleavage sites within the provirus. Multiple integrations of HTLV-I were detected in eight patients as extraordinary multiple bands; five patients showed multiple bands of the same intensity, and the remaining three showed multiple bands of differing intensities. The patients were divided into two groups based on these band patterns. One group was considered to exhibit one tumour cell clone carrying multiple copies of the provirus, whereas the other was considered to exhibit multiple tumour cell clones, each carrying one copy of the provirus. The former group of patients manifested a highly aggressive clinical course with frequent peculiar organ infiltrations, including the retina, uvea and muscle, along with the presence of large peripheral leukaemic T cells having flower-like nuclei. The latter group demonstrated an indolent clinical course with skin lesions or small leukaemic T cells having cleaved or lobulated nuclei. These findings suggest that the pattern of multiple HTLV-integrations into the tumor cell(s) has clinical implications in ATL. This may help to explain the heterogeneity of this disease.

Adult↗
PubMed1996

The CDKN2 gene alterations in various types of adult T-cell leukaemia.

The CDKN2 gene, encoding the cyclin-dependent kinase-4 inhibitor p16, is a putative tumour-suppressor gene because it is frequently altered in many malignant tumours. We analysed the CDKN2 gene in 44 cases of adult T-cell leukaemia (ATL) by Southern blot analysis, polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis, and direct sequencing. Southern blot analysis detected a homozygous deletion of the CDKN2 gene in 5/44 patients (11.4%). Mutational analysis by the PCR-SSCP method and direct sequencing showed one nonsense mutation at codon 72 (nucleotide 232), and two missense mutations at codon 43 (nucleotide 146) and codon 97 (nucleotide 309, 3/44, 6.8%). Therefore we found changes in the CDKN2 gene, including point mutations, in 18.2% of the patients with ATL. Interestingly, most of these patients had acute type ATL. Our results suggest that the CDKN2 gene is inactivated not only by homozygous deletion but also by point mutation, and these alterations contribute to the aggressiveness of ATL.

Adult↗
PubMed1997

Analysis of p18INK4C in adult T-cell leukaemia and non-Hodgkin's lymphoma.

p18INK4C, a cyclin-dependent kinase inhibitor, is a homologue of p15INK4B and p16INK4A which are frequently altered in a variety of malignancies. We searched for structural alterations of the p18INK4C gene in 44 adult T-cell leukaemias (ATLs), 101 non-Hodgkin's lymphomas (NHLs), two polyclonal B-cell proliferations, seven ATL cell lines and seven leukaemia/lymphoma cell lines, by Southern blot and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analyses. No genomic alterations of the p18INK4C gene were found in any of the samples. By RT-PCR, p18INK4C was not expressed in three of five ATL cell lines, whereas it was expressed in all the non-ATL leukaemia/lymphoma cell lines. Tax did not inhibit the expression of p18INK4C in tax-expressing Jurkat cells.

Adult↗
PubMed1998

Circulating interleukin-6 levels are elevated in adult T-cell leukaemia/lymphoma patients and correlate with adverse clinical features and survival.

We measured the circulating levels of interleukin (IL)-6 in adult T-cell leukaemia/lymphoma (ATL) patients using an enzyme-linked immunosorbent assay. The IL-6 levels in 59 ATL patients (median 8.2 pg/ml; range < 1.0 to 185.7 pg/ml) were significantly higher than in 30 healthy controls (median < 1.0 pg/ml; range < 1.0 to 3.5 pg/ml) (P < 0.0001) or 32 human T-lymphotropic virus type-I (HTLV-I) carriers (median 4.2 pg/ml: range < 1.0 to 13.3 pg/ml) (P = 0.002). Among the ATL patients, the IL-6 levels in the acute- or lymphoma-type patients were significantly higher than those in the chronic-type patients (P < 0.0001). The IL-6 levels were also higher in the patients with B symptoms than in those without B symptoms (P = 0.039), and were significantly correlated with increased serum lactate dehydrogenase (LDH) (P = 0.0004) and C-reactive protein (CRP) (P < 0.0001) and decreased serum albumin (P = 0.0003) values. The patients with elevated IL-6 levels had inferior overall survival periods compared to those with normal IL-6 levels (P = 0.025). ATL is a single disease entity, although its clinical features are quite diverse; the increased production of cytokines may cause the diversity of clinical features. The results of our study indicate that IL-6 is one such cytokine.

Adult↗
PubMed1998

Arsenic trioxide inhibits growth of human T-cell leukaemia virus type I infected T-cell lines more effectively than retinoic acids.

Adult T-cell leukaemia (ATL) is difficult to cure using conventional therapies. Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T-cell leukaemia virus type I (HTLV-I) infected T-cell lines and fresh ATL cells by arsenic trioxide (As2O3) were evaluated by comparison with a series of RA derivatives. Proliferation of four HTLV-I-infected T-cell lines was significantly reduced within 72 h by 1.0 micromol/l As2O3. Growth of two out of four HTLV-I-infected T-cell lines was also inhibited by 1.0 micromol/l RA, but to a lesser extent than by As2O3. The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by AS2O3, but far less by RA. As described in patients with acute promyelocytic leukaemia, 1.0 micromol/l of As2O3 can be safely achieved in the serum of patients; however, it is difficult to maintain this concentration of RA. In conclusion, As2O3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA.

Antineoplastic Agents↗
PubMed1999

Myelodysplastic syndrome in a patient with adult T-cell leukaemia.

A 53-year-old female who developed myelodysplastic syndrome (MDS) after chemotherapy for adult T-cell leukaemia (ATL) is described. The latent period of therapy-related MDS (t-MDS) from the time of diagnosis of ATL was approximately 35 months. Cytogenetic analysis of the bone marrow cells at the time of diagnosis of t-MDS revealed a clonal abnormality; 46,XX,add(7)(p13), der(17)t(3;17)(p11;p13). Although monoclonal integration of human T lymphotropic virus type I (HTLV-I) proviral DNA was detected in the peripheral blood lymphocytes at ATL diagnosis, bone marrow cells at t-MDS diagnosis did not show monoclonal integration of HTLV-I. To our knowledge, this is the first report of t-MDS associated with ATL.

Adolescent↗
PubMed2001

Increased lactate production follows loss of mitochondrial membrane potential during apoptosis of human leukaemia cells.

Acute tumour-lysis syndrome (ATLS) is a frequently fatal complication after cytoreductive leukaemia therapy. Lactic acidosis is associated with ATLS and its extent is correlated with the severity of ATLS. In the course of cytoreductive therapy, apoptosis is induced in tumour cells, which results in loss of mitochondrial function. We hypothesize that loss of mitochondrial function leads to compensatory glycolysis, which is the main cause of lactate accumulation and acidosis. We tested this hypothesis using the model of glucocorticoid-induced apoptosis in the human acute lymphoblastic leukaemia cell line CCRF-CEM. After induction of glucocorticoid-induced apoptosis, a biphasic course of lactate production was observed. Prior to the onset of apoptosis, i.e. prior to the loss of membrane potential, lactate production was reduced. However, subsequent to loss of mitochondrial membrane potential a massive increase in lactate production was observed (15.5 +/- 0.5 versus 10.17 +/- 0.09 mmol/10(6) cells, P = 0.001). We also demonstrated that inhibition of respiratory chain activity by antimycin A resulted in excess lactate production. In the model cell line used, conditional bcl-2 expression delayed glucocorticoid-induced apoptosis by protecting against loss of mitochondrial membrane potential; bcl-2 expression delayed the increase in lactate production and had no effect on the pre-apoptotic drop in lactate production. Apoptosis-induced lactate production was also observed in other cell lines (HL60, THP1 and OPM2) with various cytotoxic agents [doxorubicin, gemcitabine and vumon (VM26)]. Thus, the data suggest that lactate acidosis can be caused by apoptotic loss of mitochondrial function and massive apoptosis of a tumour mass via lactic acidosis may be the essential pathological event in ATLS.

Antineoplastic Agents, Hormonal↗
PubMed2001

Association of CD40 ligand expression on HTLV-I-infected T cells and maturation of dendritic cells.

Human T lymphotropic virus type I (HTLV-I) induces HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia (ATL). The development of HAM/TSP is associated with rapid maturation of dendritic cells (DCs), while ATL is accomplished with their maturation defect. The DC maturation is induced by cell-to-cell contact with CD4+ T cells expressing CD40 ligand (L). We determined the influence of CD40L expressed on various HTLV-I-infected T cells on the DC maturation. Around 60% of CD4+ T cells infected with HTLV-I for 1 week, expressed CD40L molecules involved in DC maturation. DCs matured by the CD40L+ T cells activated autologous CD4+ and CD8+ T cells. HTLV-I-immortalized T-cell lines established from healthy donors consistently expressed CD40L molecules for 3 months, however, some lines lost the expression soon thereafter. Interleukin (IL)-2-independent and transformed lines lacked that expression. Furthermore, T cells obtained from HAM/TSP patients expressed CD40L molecules for at least 3 weeks, whereas T cells from ATL patients did not express that. The CD40L T cells did not induce DC maturation, and required exogenous CD40L molecules for maturation. The CD40L+ T-cell-induced maturation was blocked by anti-CD40L antibody. Therefore, the lack of CD40L expression on HTLV-I-infected T cells may be associated with the development of ATL.

CD4-Positive T-Lymphocytes↗
PubMed2003

Lipoxins: pro-resolution lipid mediators in intestinal inflammation.

Many inflammatory processes are self-limiting, suggesting the existence of endogenous anti-inflammatory mechanisms. Among the lipid mediators generated during cell-cell interactions are the lipoxins (LX, including LXA(4) and B(4)), a distinct class of lipoxygenase-derived eicosanoids. Aspirin acetylation of cyclooxygenase 2 also promotes the generation of a series of 15-epimers of LXA(4), known as aspirin-triggered lipoxins (ATL), that may account for some of the bioactivity profile of aspirin and possibly of nonsteroidal anti-inflammatory drugs. Native LX are rapidly inactivated in vivo, and stable analogs of LXA(4), LXB(4), and ATL have been synthesized that possess enhanced bioavailability and potency as anti-inflammatory eicosanoids. Here, we review current in vitro, ex vivo, and in vivo evidence supporting cytoprotective and proresolution roles for LX in intestinal inflammation. LXA(4), LXA(4) analogs, and ATL analogs inhibit neutrophil chemotaxis, adhesion to epithelium, and epithelial cell chemokine release. In addition, LX blunt TNF-alpha-stimulated inflammatory responses, cyclooxygenase product generation, and epithelial cell apoptosis and are cytoprotective for cytokine-activated colonic mucosa ex vivo. LX, ATL, and synthetic LX analogs have already been demonstrated to possess impressive antiinflammatory and proresolution efficacy in a range of experimental models of inflammation in vivo. Further elucidation of the role of LX in intestinal epithelial cell biology and immune function may yield novel therapeutic approaches in inflammatory bowel disease and possibly gastrointestinal cancer.

Animals↗
PubMed1999

Patient readmission and support utilization following anterior temporal lobectomy.

The aim of this study was to examine factors precipitating patient readmission, following anterior temporal lobectomy (ATL) for refractory epilepsy. A second aim was to explore the use of hospital outpatient and community support services ('outpatient services') by this patient population. These aims served the more general goal of identifying patients most likely in need of services additional to those routinely provided by our Seizure Surgery Follow-up and Rehabilitation Programme. The medical records of 100 consecutive ATL patients were retrospectively examined for the incidence and diagnoses precipitating acute readmission, and the utilization of additional outpatient services. Twenty-one patients (21%) required readmission post-ATL, totalling 47 readmissions between them. Psychiatric diagnoses were the most prevalent (53%), including anxiety, depression and/or post-ictal psychosis. Epileptological diagnoses were the other main precipitant (28%). Additional outpatient services were predominantly utilized for ongoing psychological support. Of the 21 patients requiring readmission, 10(10%) also needed additional outpatient services. These patients were predominantly female or unemployed, in contrast to male or employed patients who tended to require readmission only. Seventeen patients (17%) were maintained within the community using additional outpatient services only. Characteristics of these patients included disrupted family dynamics, limited social networks, and/or a psychiatric history. These patients were also more frequently beyond the 24-month follow-up period of the programme. A profile of patients most in need of additional support services can be constructed to assist team planning of proactive management strategies for the rehabilitation phase of ATL.

Acute Disease↗
PubMed1990

Transactivation of interleukin 2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for immunotherapy.

A state of T-cell activation, reflected by a marked degree of spontaneous proliferation in vitro, exists among patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) but not in those with retroviral-induced adult T-cell leukemia (ATL). We wished to define the mechanism by which the immune activation of circulating cells from HAM/TSP is driven, thus gaining insight into the pathogenesis of this HTLV-I-associated disease. By using a modification of the polymerase chain reaction, we compared the levels of interleukin 2 (IL-2) and IL-2 receptor alpha chain (IL-2R alpha) mRNA expression to the transcription of the HTLV-I transactivator gene, pX, in peripheral blood mononuclear cells of HAM/TSP and ATL patients as well as seropositive carriers. Up-regulation of IL-2 and IL-2R alpha transcripts was detected in HAM/TSP and seropositive carriers that paralleled the coordinate mRNA expression of the pX transactivator. In addition, IL-2 and soluble IL-2R alpha serum levels in HAM/TSP and seropositive carriers were elevated. Despite markedly elevated levels of soluble IL-2R alpha in ATL, transcripts for IL-2 and pX were not demonstrable in the circulating cells. Finally, the marked degree of in vitro spontaneous proliferation present in HAM/TSP was profoundly inhibited by specific anti-IL-2R or anti-IL-2 blocking antibodies. Collectively, these results suggest that immune activation in HAM/TSP, in contrast to ATL, is virally driven by the transactivation and coordinate expression of IL-2 and IL-2R alpha. This deregulated autocrine process may contribute to the evolution of inflammatory nervous system damage in HAM/TSP.

Base Sequence↗
PubMed1990

Adult T-cell leukemia-derived factor/thioredoxin, produced by both human T-lymphotropic virus type I- and Epstein-Barr virus-transformed lymphocytes, acts as an autocrine growth factor and synergizes with interleukin 1 and interleukin 2.

Interleukin 1 (IL-1) has been obtained from the Epstein-Barr virus-infected B-lymphoblastoid cell line 3B6 and shown to be involved in autocrine growth of 3B6 B cells. Independently, adult T-cell leukemia-derived factor (ADF) was purified from human T-lymphotropic virus I-infected leukemic T-cell line (ATL-2) and reported as an interleukin 2 (IL-2) receptor-inducing factor. We have previously reported the same molecular mass, pI, and NH2-terminal amino acid sequence for both 3B6-derived IL-1 and ADF. cDNA cloning of ADF demonstrated high homology with the prokaryotic disulfide reducing enzyme thioredoxin. We show here that ADF and 3B6-derived IL-1 are identical. By RNA blot, 3B6 and ATL-2 cells were shown to contain high levels of 0.6-kilobase mRNA corresponding to ADF. Such message was not detected in resting peripheral blood lymphocytes but could be weakly induced by lymphocyte activation. Antibodies have been raised against synthetic peptides corresponding to the NH2 terminus and the COOH terminus of ADF. Immunoblotting and sequential immunoprecipitation with these antibodies revealed the same 13-kDa protein in 3B6 and ATL-2 cells. Recombinant ADF could sustain growth of 3B6 and ATL-2 cells at low cellular concentration without fetal calf serum; ADF, thus, appears involved in their autocrine growth. Similarly, recombinant ADF could enhance growth of other B-cell lines, including the Epstein-Barr virus-negative Burkitt lymphoma line BL41 and the lymphoblastoid cell lines CRAG8, CRB95, and 1G8. Finally, recombinant ADF exhibits marked synergism with other cytokines, such as IL-1 and IL-2, allowing virally infected lymphocytes to respond to suboptimal amounts of a variety of growth factors.

B-Lymphocytes↗
PubMed1992

Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers.

Although human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), the role of viral gene expression in the progression to and maintenance of the leukemic state in vivo is unclear because of the inability of most previous studies to readily detect HTLV-I RNA in infected individuals. By using the reverse transcriptase-polymerase chain reaction, we detected spliced messages for the HTLV-I pX regulatory genes in primary uncultured cells from ATL patients and healthy asymptomatic carriers. In addition to the expected doubly spliced pX message, three alternatively spliced mRNAs were demonstrated (pX delta 17, pX-p21rex, and pX-orfII mRNAs, where orf = open reading frame). The same splice sites were shown in the messages from uncultured ATL cells and from the HTLV-I-producing C10/MJ cell line. Alternatively spliced pX mRNAs have the potential to code for known and putative pX gene products. Among the transcripts is a monocistronic mRNA likely to code for p21rex (pX-p21rex mRNA). Since alternative splicing of HTLV-I pX mRNA can be found in primary uncultured cells, it is likely to have a functional significance in vivo. This suggests possible roles for HTLV-I gene expression in the progression to and maintenance of ATL, as well as in the phase preceding it.

Base Sequence↗