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)

Interleukin-2 (IL-2) is a lymphokine synthesized by T cells following activation. Resting T cells do not express IL-2 receptors, but receptors are rapidly expressed on T cells following interaction of the antigen-specific T-cell receptor complex with appropriately processed and presented antigens. Anti-Tac, a monoclonal antibody that recognized the IL-2 receptor, has been used to purify the receptor. The recognized the IL-2 receptor, has been used to purify the receptor. The receptor is a 55-Kd glycoprotein comprised of 272 amino acids including a single 19-amino transmembrane domain and a short intracytoplasmic domain composed of 13 amino acids at the carboxy terminus. Normal resting T cells and most leukemic T-cell populations examined did not express IL-2 receptors; however, the leukemic cells of all patients with human T-cell lymphotrophic virus (HTLV-I)-associated adult T-cell leukemia (ATL) expressed the Tac antigen. In HTLV-I-infected cells, the 42-Kd long open reading frame (tat) protein encoded in part by the tat region of HTLV-I may act as a transacting activator that induces transcription of the IL-2 receptor gene, thus providing an explanation for the constant association of HTLV-I infection of lymphoid cells and IL-2 receptor expression. The constant display of large numbers of IL-2 receptors which may be aberrant in the ATL cells may play a role in the uncontrolled growth of these leukemic T cells. Patients with the Tac-positive ATL are being treated with both unmodified and toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor.
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PMID:The interleukin-2 receptor on normal and malignant lymphocytes. 288 69

A unique T-cell line, designated ATL-5T, was established from lymphoma cells in pericardial effusion of an adult T-cell leukemia (ATL) patient not carrying HTLV-1 provirus. The cell line is OKT4 and/or Leu3a+ and OKT8 and/or Leu2a+, but interleukin 2 receptor (IL2R)- and HTLV-1 provirus genome negative, and has cytogenetically abnormal karyotypes. The cell line contains rearranged T-cell receptor beta-chain gene, which was identical in rearrangement pattern to the T-cell receptor beta-chain gene in primary cells. These results suggest that factors other than HTLV-1 may sometimes be associated with HTLV-1-negative ATL. The ATL-5T cell line we describe here is unique, and should contribute to further elucidation of the mechanisms involved in the pathogenesis of HTLV-1-negative ATL and HTLV-1-positive ATL.
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PMID:A unique T-cell line derived from an HTLV-1-negative adult T-cell leukemia patient. 289 Jun 13

Abnormal expression of the low-affinity receptor for interleukin-2 (IL-2R) is a characteristic of the HTLV-I (+) leukemic T cells in adult T-cell leukemia (ATL). Despite the expression of IL-2R bearing Tac antigen (IL-2R/p55), leukemic cells of the majority of ATL patients do not proliferate in response to IL-2. In the human NK cell line, YT, as well as in ATL-derived T cells, the co-expression of IL-2R/p55 and the second IL-2R without the Tac epitope (IL-2R/p70) is required to produce high-affinity IL-2R. To study the effect of HTLV-I on both of the IL-2Rs, we transfected a fragment of HTLV-I containing the p40X gene into YT cells. One of the 2 transfected YT clones (YT/pX-5.1) had an increased level of expression of IL-2R/p55. In contrast, expression of IL-2R/p70 was unaffected, as determined by Scatchard analysis and the cross-linking study using 125I-IL-2. Our results show that the T-cell phenotype is not required for induction of IL-2R/p55 by p40X. We suggest that HTLV-I infection induces a disproportionate induction of IL-2R/p55 without significant enhancement of IL-2R/p70 expression, resulting in the predominant expression of low-affinity IL-2R in ATL. IL-2R/p70 may be a critical parameter determining the IL-2 reactivity of HTLV-I-infected T cells as well as of normal lymphocytes.
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PMID:Differential effects on expression of IL-2 receptors (p55 and p70) by the HTLV-I pX DNA. 289 42

Using an enzyme-linked immunosorbent assay (ELISA) technique, we measured the soluble interleukin 2 receptor (s-IL-2R) levels in the sera of patients with adult T-cell leukemia (ATL) in Japan. The s-IL-2R levels in the sera of the ATL patients were markedly higher (range 540-310, 400 U/ml, mean +/- SD = 62,800 +/- 81,000 U/ml, n = 42) than those in normal individuals (range 42-950 U/ml, mean +/- SD = 322 +/- 198 U/ml, n = 35, P less than 0.01). The patients with acute-type or lymphoma-type ATL had high s-IL-2R levels (range 11,900-310,400 U/ml, mean +/- SD = 110,340 +/- 370 U/ml, n = 15; range 26,400-214,400 U/ml, mean +/- SD = 90,170 +/- 59,040 U/ml, n = 7, respectively). All of the patients with hypercalcemia (Ca greater than 10 mg/dl) or elevated serum LDH levels (LDH greater than 500 IU/liter) also had s-IL-2R levels above 10,000 U/ml. The high s-IL-2R levels in the sera of ATL patients indicate abnormal IL-2 receptor production and its release from the leukemic cells in vivo. Thus, the serum s-IL-2R level may be a sensitive and useful marker to monitor the total amount of tumor cells in ATL, especially in the lymphoma type. We next examined the serum s-IL-2R levels in human T-cell leukemia/lymphoma virus type-I (HTLV-I) seropositive healthy carriers to investigate whether there might be abnormal IL-2 receptor expression in such individuals. However, there was no statistically significant difference between the s-IL-2R level of 71 HTLV-I seropositive healthy carriers (range 65-880 U/ml, mean +/- SD = 394 +/- 212 U/ml) and that of 71 age- and sex-matched normal individuals (range 33-950 U/ml, mean +/- SD = 357 +/- 224 U/ml) who lived in Okinawa Prefecture.
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PMID:Serum soluble interleukin-2 receptor levels in patients with adult T-cell leukemia and human T-cell leukemia/lymphoma virus type-I seropositive healthy carriers. 290 Feb 31

A human leukemia cell line (TALL-101) was established from the bone marrow of a patient with an undifferentiated acute T cell leukemia using the conditioned medium (CM) of the human T cell leukemia virus (HTLV) II-transformed human cell line J-LB1. Immunofluorescence analysis on the original leukemic cells indicated the presence of T cell markers (Leu-1, Tdt, and T11); however, the established TALL-101 cell line expressed only antigens commonly present on progenitor cells, thymocytes, and myelomonocytic cells, but not on mature T cells. A high percentage of TALL-101 cells displayed the Tac antigen which was down-regulated upon incubation in the presence of recombinant human (rH) interleukin 2 (IL 2). Interferon (IFN)-gamma induced the appearance of class II histocompatibility leukocyte antigens (HLA) and of a T cell marker (3A1), and enhanced the expression of transferrin receptors on these cells. Further evidence for a T cell lineage of the TALL-101 cell line was provided by both chromosomic and genotypic analysis showing a translocation in chromosome 14 typical of T cell leukemias, and a rearrangement of the T-beta receptor locus. The growth-promoting activity in the J-LB1-CM was identified as granulocyte-macrophage colony stimulatory factor (GM-CSF), a growth factor which stimulates proliferation of normal myelomonocytic cells and other progenitor cells, but not known to have an effect on T cells. Dose response curves of [3H]thymidine incorporation and growth indicated that TALL-101 cells were sensitive to very low concentrations of rHGM-CSF, 5 ng/ml inducing maximal proliferation in chemically defined medium. The TALL-101 cell line is strictly GM-CSF-dependent for growth: upon depletion of GM-CSF from the culture medium, the cells stop proliferating immediately and die within 1 to 2 wk. The overall data, showing that GM-CSF is able to support the growth of a highly undifferentiated T cell leukemia, strongly suggests that this factor might have similar growth promoting effects on other immature T cell leukemias, and possibly, on normal T cell progenitors.
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PMID:Establishment and characterization of an undifferentiated human T leukemia cell line which requires granulocyte-macrophage colony stimulatory factor for growth. 295 97

A case of T cell prolymphocytic leukaemia of helper/inducer T cell phenotype with IgM hypergammaglobulinaemia in a 65-year-old Saudi man is presented. The neoplastic T cells in the patient had an OKT3+, OKT4+, OKT8-, OKT11+, OKCLL+, OKIa1+, OKDR+, Tac+ phenotype. The presence of OKIa1+, OKDR+, and Tac+ antigens indicates that the leukaemic T cells were in an activated state. The cells responded to phytohaemagglutinin, but showed a diminished response to concanavalin A. The reduced interleukin 2 receptor expression and interleukin 2 production were associated with defective concanavalin A-induced proliferation. There was suppression of mixed lymphocyte culture reaction between the patient and two healthy donors in response to concanavalin A. In vitro immunoglobulin production experiments demonstrate that the leukaemic T cells provided an enhanced helper cell function to produce IgM, and suppressor cell function to produce IgG immunoglobulins by pokeweed mitogen-induced normal B lymphocyte differentiation. In this study we also found that the patient's T cells proliferate in response to lipopolysaccharides, thus providing the first evidence that leukaemic (OKT4+) T cells from a prolymphocytic leukaemia patient can be stimulated by lipopolysaccharides.
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PMID:Functional properties of neoplastic T cells in helper T cell prolymphocytic leukaemia with IgM hypergammaglobulinaemia. 296 72

Human T-cell leukemia virus (HTLV)-infected cell lines derived from adult T-cell leukemia (ATL) express constitutively the receptor for Interleukin-2 (IL-2-R) and the associated antigen (Tac antigen). In contrast, the same antigen is transiently expressed by normal T-cells only after immune stimulation. Recently, it was reported that the constitutively expressed Tac antigen on ATL cells and cell lines was not down-regulated or modulated by anti-Tac antibody. Since the antigen was modulated on normal mitogen- or alloantigen-stimulated T-cells, we postulated that the regulation of IL-2-R may be abnormal on ATL cells; the synthesis of IL-2-R is continuously stimulated in these cells. A unique HTLV/ATLV(-) cell line (YT) derived from a child with acute lymphoblastic leukemia was found to express low levels of Tac antigen that could be enhanced by various stimuli, including conditioned medium (CM) derived from normal lymphocytes, but not by lectins (PHA, Con A). Of particular interest, the exposure of YT cells to CM from ATL cell lines with helper phenotype revealed the presence of factor(s) (ATL-derived factor, ADF) that augmented the synthesis and expression of IL-2-R/Tac antigen on YT cells and promoted YT cell growth. CM from HTLV(-) leukemia cell lines lacked both IL-2-R augmenting activity and a growth promoting activity. Immunoaffinity-purified IL-2 and recombinant gamma interferon also lacked IL-2-R augmenting activity. Moreover, the physicochemical analysis with Fast protein liquid chromatography (FPLC) revealed that ADF was quite different in pI point from the IL-2-R augmenting activity in CM from normal lymphocytes. These results suggested that ADF is a unique product of HTLV(+) cells. The possible relationship between ADF production, HTLV infection, and the abnormal expression of IL-2-R is suggested, and these abnormalities may be advantageous for the leukemogenesis and abnormal growth of ATL.
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PMID:Adult T leukemia cells produce a lymphokine that augments interleukin 2 receptor expression. 297 23

The localization of Tac antigen in adult T-cell leukemia-associated antigen (ATLA)-positive lymphomas was studied ultrastructurally with the use of the immunoperoxidase technique. The antigen was observed on the plasma membranes of a portion of the characteristic cells with convoluted nuclei and a majority of the cells with less irregular nuclei, which were larger than the former. In addition, the cisternae of the rough endoplasmic reticulum, perinuclear cisternae, and Golgi cisternae of the latter cells were also positively stained with anti-Tac antibody. It is thought that the positive reaction of the plasma membranes may correspond to interleukin 2 (IL 2) receptors, the cytoplasmic and perinuclear reaction sites may well correspond to the precursor of IL 2 receptors, and Tac antigen may be produced in the cytoplasm of the ATLA-positive lymphoma cells.
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PMID:Immunoelectron-microscopic localization of Tac antigen in adult T-cell leukemia/lymphoma. 299 Feb 20

Interleukin-2 (IL-2) is a lymphokine synthesized by some T-cells following activation. Resting T-cells do not express IL-2 receptors, but receptors are rapidly expressed on T-cells following interaction of antigens, mitogens, or monoclonal antibodies with the antigen-specific T-cell receptor complex. Using anti-Tac, a monoclonal antibody that recognizes the IL-2 receptor, the receptor has been purified and shown to be a Mr 33,000 peptide that is posttranslationally glycosylated to a Mr 55,000 mature form. Normal resting T-cells and most leukemic T-cell populations do not express IL-2 receptors; however, the leukemic cells of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the Tac antigen. In human T-cell lymphotropic virus-I infected cells, the Mr 42,000 long open reading frame protein encoded in part by the pX region of this virus may act as a transacting transcriptional activator that induces IL-2 receptor gene transcription, thus providing an explanation for the constant association of IL-2 receptor expression with adult T-cell lymphotropic virus-I infection of lymphoid cells. The constant expression of large numbers of IL-2 receptors which may be aberrant may play a role in the uncontrolled growth of adult T-cell leukemia cells. Two patients with Tac-positive adult T-cell leukemia have been treated with the anti-Tac. One of the patients had 6- and 3-mo remissions of his leukemia following two courses of therapy with this monoclonal antibody directed toward this growth factor receptor.
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PMID:Interleukin 2 receptor (Tac antigen) expression in HTLV-I-associated adult T-cell leukemia. 299 Jun 87

Sera obtained from patients with systemic lupus erythematosus (SLE) were tested for their reactivity to cell lines derived from cutaneous T-cell lymphoma (CTCL), or adult T cell leukaemia (ATL), and with other cell lines, by indirect immunofluorescence method. Approximately one half of SLE sera reacted with the surface antigens of HUT-102 cells, a cell line from CTCL, which constitutively expresses Tac antigen. The titre tended to be higher in the active than in the inactive stage. These positive sera also reacted with other neoplastic or normal T cell lines having Tac antigen. SLE sera reacting with HUT-102 surface antigens were further examined for their reactivities to Tac antigen, the putative IL-2 receptor, using HUT-102 or ATL-2. Pretreatment with anti-Tac monoclonal antibody partially blocked the reactivities to HUT-102 surface antigens in nine of 15 SLE sera tested. The binding of 125I-labelled anti-Tac monoclonal antibody was displaced by the addition of sera from six of 15 SLE patients. In addition, nine of the 15 SLE sera could inhibit the binding of 125I-labelled IL-2 to ATL-2 cells. These results suggested that some of SLE sera contained antibodies against the IL-2 receptor.
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PMID:Systemic lupus erythematosus sera antilymphocyte reactivity: detection of antibodies to Tac-antigen positive T cell lines. 300 53


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