Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interleukin-1 receptor antagonist (IL-1ra or IRAP) is a small, acidic glycoprotein that competitively inhibits the biological activities of interleukin-1 (IL-1). Alternative splicing gives rise to secreted and intracellular forms of IL-1ra. Both forms block cellular responses to IL-1 by occupying IL-1 receptors without triggering an agonist response. The affinity of IL-1ra for the type I IL-1 receptor is approximately that of IL-1. However, because of IL-1's pronounced "spare receptor" effect, IL-1ra is a weak inhibitor of biological responses to IL-1. The value for the affinity constant of IL-1ra's binding to the type II IL-1 receptor has been the subject of disagreement. However, recent data suggest that human IL-1ra has only weak affinity for the human type II receptor. This is consistent with the likelihood that the type II receptor plays no role in signal transduction, instead being a "decoy" that can be shed as a soluble receptor with the ability bind, and thus inhibit, IL-1. Under the name Antril, IL-1ra is being tested in clinical trials of a number of human diseases where IL-1 plays a major pathophysiologic role. These diseases include sepsis, rheumatoid arthritis, chronic myelogenous leukemia, and asthma, among others. Although IL-1ra has clear pharmacologic potential in such conditions, its application in chronic diseases is limited by difficulties associated with delivering proteins as drugs. As an alternative, we have suggested transfer of the gene coding for IL-1ra; strategies for both local and systemic gene delivery are being developed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The interleukin-1 receptor antagonist and its delivery by gene transfer. 803 9

Alleles of the IL-1 genes are associated with several autoimmune and inflammatory diseases, where they tend to have a role in the severity of the disease rather than in susceptibility to the disease itself. Allele 2 of the variable number tandem repeat (VNTR) polymorphism in the IL-1 receptor antagonist (IL-1ra) gene was the first marker of the IL-1 cluster to be associated in this way with severity of chronic, systemic and local inflammatory diseases. Because of the role that IL-1 also plays in the pathobiology of certain hematopoietic disorders, we aimed at examining the allelic distribution of the IL-1ra VNTR in leukemias, lymphomas and related malignancies. While in patients with chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), multiple myeloma (MM) and related disorders, primary acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and Hodgkin's disease (HD), the allelic distribution of IL-1RN was comparable to that seen in healthy control subjects, in a small group of patients with secondary AML the frequency of the IL-1RN*4 allele appeared to be significantly increased.
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PMID:Polymorphism within the second intron of the IL-1 receptor antagonist gene in patients with hematopoietic malignancies. 938 10

To estimate intracellular interleukin-1 receptor antagonist (icIL-1ra) expression in the bone marrow cells from adult patients with chronic myelogenous leukemia (CML), flow cytometry (FCM) assay was used for detecting the mean icIL-1ra fluorescence intensity per cell (equivalent to it's expression level) in different groups of cells from normal and CML patient bone marrows by 15 monoclonal antibodies with different fluorescent marker. The results showed that all of marrow nucleated cells express IL-1ra, but its expression level in granulocytes was the highest and that in lymphocytes was the lowest. The icIL-1ra expression level was significantly lower in nucleated marrow cells, granulocytes and lymphocytes from the marrow of 17 untreated CML patients than that from the marrow of 8 normal. The mean icIL-1ra fluorescence intensity was significantly lower in marrow nucleated cells, granulocytes and lymphocytes in 13 CML patients with marrow blasts >or= 10% than that in 43 CML patients with marrow blasts < 5% or than that in 9 CML patients with marrow blasts 5% - 10%. It was concluded that the lower expression of icIL-1ra in CML marrow nucleated cells might be involved in the evolution of CML.
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PMID:[The significance of intracellular IL-1ra expression in the bone marrow cells from adult chronic myelogenous leukemia]. 1266 86