Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of interleukin-2 receptors (IL-2R) was examined in 328 adult patients with non-T-cell (non-T) acute leukaemia and blast crisis of chronic myelocytic leukaemia (CML.BC) using two monoclonal antibodies, anti-Tac for IL-2R alpha chain (IL-2R alpha) and Mik beta 1 for IL-2R beta chain (IL-2R beta). Leukaemic cells in the following cases were positive for anti-Tac; 28/192 of acute myelocytic leukaemia (AML), 24/44 CML-BC, 4/28 CD19(+)CD10(-) acute lymphoblastic leukaemia (ALL), and 20/64 common ALL (c-ALL). IL-2R beta was not detected on leukaemic cells of any case examined. Eleven of IL-2R alpha(+) AML were derived from myelodysplastic syndrome. None of the IL-2R alpha positive leukaemic cells responded to exogenous recombinant human IL-2 (rhIL-2) in culture. In addition, IL-2R alpha expression on non-T leukaemic cells was closely correlated with coexpressing different lineage markers and the presence of the Philadelphia abnormality. Marked increase of serum soluble IL-2R alpha was demonstrated in the IL-2R alpha(+) patients examined. Clinically, the IL-2R alpha(+) patients showed significantly lower response to chemotherapy and poorer prognosis than IL-2R alpha(-) patients. Our results clearly indicate the diagnostic importance of IL-2R alpha expression in non-T acute leukaemia with a close relation to the particular cellular characteristics and the prognosis.
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PMID:Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells. 158 Dec 11

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

We determined nine immune function parameters at diagnosis in patients with myelodysplastic syndromes (MDS) and correlated the results with the FAB classification and prognosis by univariate and multivariate analyses. Patients with refractory anaemia (RA) and refractory anaemia with ring sideroblasts (RAS) tended to have a higher CD4/CD8 ratio and a lower amount of gamma-globulins and soluble interleukin-2 receptors in serum in comparison to those suffering from the other three subgroups of MDS. FAB classification, neutrophil and CD8+ T-cell number had the best discriminatory capacity for predicting survival less than 1 year, and FAB classification, neutrophil number and serum TNF levels were predictors for conversion to acute leukaemia. The frequent occurrence of infections, on the other hand, could be better predicted by the absolute numbers of neutrophils and CD4+ cells and by the skin test score.
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PMID:Immune function parameters at diagnosis in patients with myelodysplastic syndromes: correlation with the FAB classification and prognosis. 195 86

Previously, cloning efficiencies and mitogenic responsiveness of lymphocytes from patients with preleukemic disorders were shown to be significantly depressed. Whole blood T lymphocyte colony formation and 3H-TdR incorporation were used to assess the effects of interleukin-2 (IL-2) and thymopoietin (TP-5) on the proliferation of lymphocytes from patients with preleukemia. There were no statistically significant differences (p greater than 0.05) between any of the test groups stimulated with mitogen alone when compared to groups stimulated with mitogen plus TP-5 and/or IL-2 in either assay system for either patient or control groups. Nevertheless, TP-5 and IL-2 markedly increased the cloning efficiency and mitogenic responsiveness of lymphocytes from many of the patients studied, but in no case restored the proliferation response to the level of mitogen stimulated control lymphocytes. These findings suggest that other soluble mediators/factors may be needed to fully compensate for deficient mitogenic responsiveness and colony formation of lymphocytes from patients with preleukemic disorders which may be multifactoria in origin. Of importance, enhancement of lymphocyte responsiveness to PHA/Con-A with TP-5 and IL-2 suggests the presence of maturational/functional defects in lymphocytes from some of these patients which may be compensated for in part by addition of TP-5 and IL-2.
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PMID:Effect of thymopoietin and interleukin 2 on depressed mitogenic responsiveness and colony formation of lymphocytes from patients with preleukemia. 348 54

Recent clinical studies suggested that interleukin-2 (IL-2) has therapeutic potential for some hematologic malignancies, but the therapeutic role of IL-2 for myelodysplastic syndrome (MDS) is still unclear. MDS is a clonal malignant disorder which often involves a variety of immunologic abnormalities. Examination of the effects of IL-2 on MDS in vitro yielded the following results: (1) IL-2 did not induce the proliferation of blasts in most MDS cases. (2) The cytotoxicity of IL-2-induced lymphokine-activated killer (LAK) cells for cell lines and MDS blasts was reduced in the high-risk MDS group (refractory anemia with excess blasts (RAEB), RAEB in transformation and MDS transformed to acute leukemia), but it was still preserved in the low-risk MDS group (refractory anemia (RA) and RA with ringed sideroblasts). However, considerable variation in LAK cell cytotoxicity was noted in each group. (3) The reduced LAK cell cytotoxicity observed in MDS was explained, at least in part, by the presence of a reduced of number of natural killer (NK) cells amongst the LAK cells. (4) MDS patients who have a high blood soluble IL-2 receptor (sIL-2R) level often had defects in NK and CD8+ T cells. These in vitro findings suggest that the response to IL-2 is heterogeneous in MDS patients, and those who have a low-risk MDS subtype and/or a low blood sIL-2R level, may be prone to respond to IL-2 therapy. Clinical trials are mandatory in order to elucidate the efficacy of IL-2 therapy in the treatment of MDS.
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PMID:Interleukin-2 therapy for myelodysplastic syndrome: does it work? 754 31

Aggressive chemotherapy of advanced myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) evolving from MDS, subacute AML and secondary AML has usually been associated with low complete remission (CR) rates, a high incidence of early death, and low disease-free survival. We therefore have initiated a phase-III trial of aggressive chemotherapy consisting of idarubicin, cytosine arabinoside, and VP-16 to improve the CR rate. Each chemotherapy cycle is followed by G-CSF to accelerate neutrophil recovery and to reduce the incidence of infections. Until now, 19 patients with high-risk AML have been entered. The CR rate is 47%, with only one death during induction. Patients achieving CR are randomized to receive either high-dose or low-dose interleukin-2 to eliminate residual leukemic cells and to prolong the duration of remission.
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PMID:Aggressive chemotherapy combined with G-CSF and maintenance therapy with interleukin-2 for patients with advanced myelodysplastic syndrome, subacute or secondary acute myeloid leukemia--initial results. 768 47

Signal transduction through the T-cell receptor and cytokine receptors on the surface of T lymphocytes occurs largely via tyrosine phosphorylation of intracellular substrates. Because neither the T-cell receptor nor cytokine receptors contain intrinsic kinase domains, signal transduction is thought to occur via association of these receptors with intracellular protein tyrosine kinases. Although several members of the SRC and SYK families of tyrosine kinases have been implicated in signal transduction in lymphocytes, it seems likely that additional tyrosine kinases involved in signal transduction remain to be identified. To identify unique T-cell tyrosine kinases, we used polymerase chain reaction-based cloning with degenerate oligonucleotides directed at highly conserved motifs of tyrosine kinase domains. We have cloned the complete cDNA for a unique human tyrosine kinase that is expressed mainly in T lymphocytes (EMT) and natural killer (NK) cells. The cDNA of EMT predicts an open reading frame of 1866 bp encoding a protein with a predicted size of 72 Kd, which is in keeping with its size on Western blotting. A single 6.2-kb EMT mRNA and 72-Kd protein were detected in T lymphocytes and NK-like cell lines, but were not detected in other cell lineages. EMT contains both SH2 and SH3 domains, as do many other intracellular kinases. EMT does not contain the N-terminal myristylation site or the negative regulatory tyrosine phosphorylation site in its carboxyterminus that are found in the SRC family of tyrosine kinases. EMT is related to the B-cell progenitor kinase (BPK), which has recently been implicated in X-linked hypogammaglobulinemia, to the TECI mammalian kinase, which has been implicated in liver neoplasia, to the more widely expressed TECII mammalian kinase, and to the Drosophila melanogaster Dsrc28 kinase. Sequence comparison suggests that EMT is likely the human homologue of a recently identified murine interleukin-2 (IL-2)-inducible T cell kinase (ITK). However, unlike ITK, EMT message and protein levels do not vary markedly on stimulation of human IL-2-responsive T cells with IL-2. Taken together, it seems that EMT is a member of a new family of intracellular kinases that includes BPK, TECI, and TECII. EMT was localized to chromosome 5q31-32, a region that contains the genes for several growth factors and receptors as well as early activation genes, particularly those involved in the hematopoietic system. Furthermore, the 5q31-32 region is implicated in the genesis of the 5q- syndrome associated with myelodysplasia and development of leukemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Identification, cloning, and characterization of a novel human T-cell-specific tyrosine kinase located at the hematopoietin complex on chromosome 5q. 836 6

We report the case of a patient treated with interleukin-2 (IL-2) for refractory anemia with excess blasts (RAEB), which developed during third complete remission of acute lymphoblastic leukemia. IL-2 was given subcutaneously at 2.5 x 10(5) IU (= 10(5) BRMP units) twice daily for 30 days. During treatment spontaneous natural killer (NK) activity was enhanced, circulating lymphokine-activated killer effector cells became detectable and CD56+/CD3- NK cells in the blood doubled. The response in the bone marrow was a reduction in myeloid blast cells (from 7 to 0%), ringed sideroblasts (from > 15 to 0%) and dysplasia (from trilineage to minimal megakaryocytic), and a decrease in metaphases with the RAEB karyotype (from 43 to 2%). Toxicity of IL-2 was minimal. Thus a relatively low dose of IL-2 caused immune activation and resulted in significant hematologic and cytogenetic response in this case of therapy-related myelodysplasia.
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PMID:Response of therapy-related myelodysplasia to low-dose interleukin-2. 844 51

To evaluate the clinical usefulness of IL-2 in myelodysplastic syndromes (MDS) the in vitro effects of interleukin-2 (IL-2) on blast cell proliferation, clonogenic activity, cytokine release and cell mediated cytotoxicity were examined in 49 MDS patients. Morphological analyses of bone marrow (BM) cytospin preparations showed a significant decrease in the number of blast cells in MDS after incubation with IL-2. Incubation of bone marrow mononuclear cells (BMMNCs) with IL-2 induced a significant increase in the number of CFU-GM in comparison with untreated controls. gamma-IFN and GM-CSF, but not alpha-TNF were found to be released in significant amounts by the BMMNCs cultured with IL-2. No significant differences in the surface phenotypes of fresh lymphocytes were observed between the normal and MDS subjects. After incubation with IL-2, we observed a significant increase in the number of CD3-/CD56+ cells in both normal and MDS subjects. Peripheral blood (PB) and BM NK activity against K562 was significantly greater in MDS after stimulation with IL-2. These data suggest the clinical usefulness of IL-2 in a large subgroup of patients as it may reduce the percentage of blasts and increase clonogenic capacity and cell-mediated cytotoxicity.
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PMID:In vitro effects of IL-2 on NK-activity, clonogenic potential, blast cell proliferation and cytokine release of MDS bone marrow patients. 868

In the past several years, interest in the immunophysiological role of the pineal gland and melatonin has grown to the extent that now their immunoregulatory role is widely recognized. Melatonin has immunoenhancing properties and it is able to counteract the immunodepression induced by acute stress, drug treatment (i.e., anticancer drugs), and viral infections. Here we review the therapeutic efficacy of melatonin alone or in combination with interleukin-2 (IL-2) in cancer patients who did not respond to standard anticancer chemotherapies and/or refused any aggressive treatment. In this review, we summarize a series of reports from 1986 through 1994 in which patients affected by metastatic solid tumors, metastatic non-small-cell lung cancer, advanced solid neoplasms, myelodysplastic syndrome, hepatocellular carcinoma, and advanced endocrine tumors were studied. The conclusion drawn from these studies is that melatonin protects against IL-2 and synergizes with the IL-2 anticancer action. This combined strategy represents a well tolerated intervention to control tumor growth. In most cases performance status and quality of life seem improved.
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PMID:The clinical neuroimmunotherapeutic role of melatonin in oncology. 875 Mar 42


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