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 increase in the serum levels of the IL-2 receptors is due to its release both in vivo and in vitro from activated cells or neoplastic cells expressing it constitutively. The diagnostic, prognostic and physiopathologic significance of the sIL-2R was investigated by testing the serum of 271 haemopathic patients in various stages of the disease. In HCL the elevated sIL-2R level has a diagnostic value. In HD the sIL-2R level appears to be directly correlated with the extent of the disease and is equally important in the follow up of patients with HCL, NHL, HD, AL and MDS, where the serum level of the soluble receptor is usually associated with the biological and clinical activity of the disease. Unlike other B lymphoproliferations, patients with Multiple Myeloma on average show only slightly elevated levels of soluble receptor with no significant differences related to the stage or evolution. As for the chronic myeloproliferative disorders, we found only slightly elevated values in ET and PV, with frankly pathological values in CML during a blastic crisis or in the accelerated phase and in MFI during the clinically active phase of the disease.
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PMID:[The soluble IL-2 receptor in malignant hemopathies]. 146 37

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

Sera of 15 healthy controls and 33 patients suffering from myelodysplastic syndromes (MDS) were investigated for soluble interleukin-2 receptor (sIL-2R) expression with a cell-free enzyme-linked immunosorbent assay (ELISA) system (T-Cell Sciences; Cambridge, U.S.A.). The upper limit of the assay is indicated with 477 U/ml. According to the FAB classification eight refractory anaemia (RA), 15 refractory anaemia with excess of blasts (RAEB), five refractory anaemia with excess blasts in transformation (RAEBt) and five chronic myelomonocytic leukaemia (CMML) were examined. None of the patients had reported infectious episodes or been under treatment with cytotoxic agents and/or cytokines within the previous 3 months. Significant differences in sIL-2R levels between RA (median 368 U/ml). RAEB (median 675 U/ml) and RAEBt (median 971 U/ml) and between RA and CMML (median 723 U/ml) were detected. Six patients, who had been under treatment with rhGM-CSF for at least 2 weeks, demonstrated a three- to sevenfold increase of sIL-2R expression compared to pretreatment levels. In kinetic evaluation of serum samples for 24 h, the increase of sIL-2R expression begins within 4 h after subcutaneous application of GM-CSF and reaches its maximum after 12 h. Our data cannot suggest whether increased sIL-2R expression is a primary event due to involvement of lymphocytes in the malignant clone or whether it results from secondary alteration of the cytokine network. Application of GM-CSF in MDS may result in improvement of altered lymphocyte function. As GM-CSF induces sIL-2R expression, a down regulation of the immune response caused by neutralization of free IL-2 cannot be excluded.
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PMID:Detection of soluble IL-2 receptor in the serum of patients with myelodysplastic syndromes: induction under therapy with GM-CSF. 175 71

A 28-year-old male was admitted to our hospital because of hepatosplenomegaly and granular lymphocytosis. His peripheral leukocyte count was 3,000/microliters with 43% of granular lymphocytes (GL). These GLs were immunologically phenotyped as CD2+CD3-CD4-CD8-CD16+CD56+HLA-DR+ and were found that TcR genes coding beta and gamma chains were not rearranged. Chromosomal analysis of his GLs stimulated with IL-2 showed 47 XY, +8. This patient was diagnosed as a granular lymphocyte leukemia of natural killer cell type. Blood chemistry showed elevation of serum GOT, GPT and LDH values. The fever persisted until administration of prednisolone was initiated. But 40 days after, high fever appeared again and the liver and spleen were extremely enlarged. Combined chemotherapy was then started but resulted in no effects. He died of hepatic failure on the 77th day from admission. 47 XY, +8, that has been reported in acute non-lymphocytic leukemia and myelodysplastic syndrome, may be related to the pathogenesis in some cases of granular lymphocyte leukemia.
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PMID:[Granular lymphocyte leukemia of natural killer cell type; association with 47 XY, +8 by interleukin 2 (IL-2)-stimulated chromosomal analysis]. 225 62

In order to maintain adequate circulating numbers of blood cells, the bone marrow must produce billions of cells each day and must be able to rapidly increase production by 10-20-fold in response to infection and hemorrhage. The existence of circulating factors that regulate this process has been suspected for over 100 years. Recently, the genes encoding these growth factors were cloned and their functions are now identified. Interleukin-3 (IL-3) acts on the most primitive hematopoietic stem cell, driving this self-renewing cell to produce progeny of all hematopoietic lineages. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the granulocyte-macrophage progenitor cell, as well as cells committed to the erythroid lineage, to differentiate. G-CSF and M-CSF stimulate the most differentiated myeloid progenitors to produce granulocytes and monocytes/macrophages, respectively. Erythropoietin stimulates the differentiation of late erythroid progenitors. In the lymphoid progenitor lineage, IL-2 stimulates T cell differentiation; IL-4 and IL-6 stimulate differentiation of B cells. The colony-stimulating factors also enhance function and cause activation of the mature cells whose production they induce. In clinical trials, these hormones have successfully ameliorated anemia in renal failure, chronic disease, and in prematurity. They have improved pancytopenias in aplastic anemia, myelodysplastic syndromes, and congenital cytopenias, and they have hastened recovery from chemotherapy and bone marrow transplantation.
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PMID:Hematopoietic hormones: from cloning to clinic. 267 59

The protein-tyrosine kinase gene Itk is expressed preferentially in T lymphoid cells of the mouse and is induced by IL-2. A related gene, Btk, is expressed in the murine B lymphoid and myeloid lineages. Because mutations in Btk and the corresponding human gene are associated with X-linked immunodeficiency syndromes, it was of interest to map Itk and its human counterpart. By Southern blot analysis of DNA from the progeny of two multilocus crosses, murine Itk was mapped to Chromosome 11. By fluorescence in situ hybridization, human ITK was mapped to 5q32-q33. Murine Itk and its human homologue lie within regions of conserved synteny that include several growth factor and growth factor receptor genes. This region in humans is frequently deleted in the myelodysplastic syndrome, suggesting possible involvement of ITK in this disorder.
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PMID:Mapping of the gene for the tyrosine kinase Itk to a region of conserved synteny between mouse chromosome 11 and human chromosome 5q. 782 87

Sera of ten healthy controls and of 15 patients with myelodysplastic syndromes (MDS) were investigated for soluble interleukin-2 receptor (sIL-2R) with a cell-free enzyme-linked immunosorbent assay (ELISA). The patients with MDS underwent treatment with IL-3: eight patients at dose levels of 250 and 500 micrograms/m2 s.c. daily for 15 days, and seven patients at the dose levels of 60 and 125 micrograms/m2 s.c. three times per week for 12 weeks. None of the patients had reported infectious episodes or been under treatment with cytotoxic drugs and/or cytokines within the preceding 2 months. sIL-2R levels were elevated in MDS patients compared with healthy controls (p < 0.001). sIL-2R increased in the high-dose treatment group from 504 +/- 68 U/ml to 731 +/- 199 U/ml (p < 0.025). The increased sIL-2R expression in MDS could be a primary event due to involvement of lymphocytes in the malignant clone or due to a secondary alteration of the cytokine network caused by chronic neutropenia. A down-regulation of the immune response caused by neutralization of free IL-2 by sIL-2R during IL-3 therapy seems possible.
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PMID:Induction of soluble IL-2 receptor in patients with myelodysplastic syndromes undergoing high-dose interleukin-3 treatment. 800 57

We report a therapy-related MDS (RAEB) patient with eosinophilia, unbalanced translocation der(7)t(1;7) (q12;q22) and lung cancer. We observed no increase in cytokine levels in serum or in the conditioned medium (CM) of peripheral T cells cultured with or without IL-2. When bone marrow (BM) cells were cultured with GM-CSF, IL-3 and SCF in a semisolid system, the colonies were exclusively eosinophilic. Cytogenetic analysis of the colony cells identified the same chromosome abnormality in all metaphases to that of BM cells. Suspension and clonogenic colony assay of BM cells cultured with various cytokines showed predominant eosinophilic growth and differentiation with GM-CSF, but not with the other cytokines examined. These findings, together with mild morphological abnormalities of eosinophils, indicate clonal involvement of eosinophils in the myelodysplastic syndrome (MDS) clone, and that the eosinophilia was derived from the neoplastic clone with the translocation and was not associated with the patient's lung cancer.
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PMID:Clonal involvement of eosinophils in therapy-related myelodysplastic syndrome with eosinophilia, translocation t(1;7) and lung cancer. 898 50

We evaluated the in vitro effects of IL-12, alone and in association with IL-2 on MDS bone marrow and peripheral blood cells. Thirty-six patients and 14 healthy subjects were studied. Natural killer-activity (NK-a) levels and lymphocyte immunophenotypes were determined in fresh bone marrow (BMMNC) and peripheral blood mononuclear cells (PBMNC), which then were resuspended in medium containing IL-2, IL-12 or IL-2 + IL-12 for 7 days. Re-evaluation of NK-a levels, lymphocyte immunophenotypes, clonogenic activity and cytokine release showed that, unlike IL-2, IL-12 did not significantly increase NK-a or CD3-/56+ cell levels in either bone marrow or peripheral blood; IL-2 + 12 led to a significant increase that fell between the values reached by each cytokine alone. IL-2 + 12 and, although to a lesser extent, also IL-12 alone induced the release of large amounts of gamma-IFN and alpha-TNF. In addition, the number of clusters particularly decreased in the samples treated with IL-2 + 12 and IL-12 alone. Clonogenic activity was not modified after stimulation with any of the treatment. These data suggest that IL-12 induces the release of inhibitory cytokines in normal as well as MDS cells and that it could be used in patients with elevated bone marrow blastosis.
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PMID:In vitro effects of IL-12 and IL-2 on NK cells, cytokine release and clonogenic activity in myelodysplastic syndromes (MDS). 932 94

The levels of IL-1 alpha, IL-2, IL-6 and TNF-alpha were measured immunoradiometrically in the sera of 82 myelodysplastic (MDS) patients at diagnosis in an attempt to identify possible relationships between serum cytokine levels and clinical and laboratory parameters of the patients. We found that serum IL-6 and TNF-alpha concentrations were significantly higher in the group of MDS patients than in the normal controls (p < 0.03 and p < 0.001, respectively), while serum IL-1 alpha and IL-2 levels did not differ statistically between patients and control subjects. Elevated serum IL-6 and TNF-alpha concentrations were mainly seen in patients with high-risk myelodysplasia (MDS), i.e. patients with chronic myelomonocytic leukemia (CMML) (p < 0.05 and p < 0.001, respectively), refractor anemia with excess of blasts (RAEB) (p < 0.01 and p < 0.001, respectively), or refrochopy anemia with excess of blasts in transformation to acute leukemia (RAEB-t) (p < 0.001 and p < 0.001, respectively). Patients with low-risk disease, i.e. patients with refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS), had serum cytokine levels comparable to those of controls. Patients' serum IL-6 and TNF-alpha correlated inversely with the hemoglobin concentration (p < 0.01 and p < 0.05, respectively) and positively with the absolute number of circulating myeloblasts (p < 0.01 and p < 0.001, respectively) and the proportion of bone marrow (p < 0.001 and p < 0.001, respectively) myeloblasts. A negative correlation was also noted between serum TNF-alpha concentrations and patients' survival in high-risk MDS (p < 0.02). We concluded that elevated serum IL-6 and TNF-alpha values are seen mainly in patients with high-risk disease, and that high serum TNF-alpha concentrations are predictive of shortened survival in this group of patients.
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PMID:Elevated serum TNF-alpha concentrations are predictive of shortened survival in patients with high-risk myelodysplastic syndromes. 970 53


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