Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A chromosome band 4q21 gene (MLLT2, formerly called AF-4/FEL) involved in a reciprocal translocation with chromosome band 11q23 in t(4;11) acute leukemia has been cloned. To provide better definition of gene order and relationships in this region where MLLT2 resides, we used pulsed field gel electrophoresis (PFGE) to investigate 13 genes (including MLLT2) with physical locations in bands 4q11-->q25. Somatic cell hybrids derived from RS4;11, a leukemic cell line carrying the t(4;11)(q21;q23), were also used to localize genes in relation to MLLT2. Linkage of the interleukin 8 (IL8), albumin (ALB), and platelet factor 4 (PF4) genes was confirmed by NotI, SalI and SacII digests. The maximum distance between PF4 and ALB is 210 kb and between ALB and IL8 is 420 kb. The alcohol dehydrogenase, class I (ADH2, ADH3) gene cluster can be linked to the alcohol dehydrogenase, class III gene (ADH5) by SacII, NruI, and EagI digests. The maximum distance between them is 590 kb. Our study indicated that ALB, alpha-fetoprotein (AFP), PF4, beta-thromboglobulin (PPBP), GRO1 (encoding a cytokine also called melanoma growth-stimulatory activity), and IL8 genes can be physically linked. In this study the gamma-interferon induced protein 10 (INP10), bone morphogenetic protein 3 (BMP3), annexin III (ANX3), KIT, amphiregulin (AREG), immunoglobulin J polypeptide (IGJ), deoxycytidine kinase (DCK) and MLLT2 genes were not linked to one another or to the above two groups of genes. Our analysis using somatic cell hybrids combined with previous reports demonstrated that the ADH gene cluster is telomeric to MLLT2 and KIT, ALB, AFP, PF4, beta TG, GRO1, IL8, ANX3, AREG and DCK are centromeric to MLLT2.
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PMID:A mapping study of 13 genes on human chromosome bands 4q11-->q25. 769 25

To date no hematopoietic progenitors of dendritic Langerhans' cells (DLC), which represent an highly efficient class of antigen presenting cells, have been identified or the cytokines they elaborate have been defined. Here we describe an acute leukemia patient whose blasts (90-96% in peripheral blood and bone marrow) had a phenotype consistent with putative progenitors of DLC. The patient was treated with ara-C and VP-16 but did not achieve remission. The blasts had lobulated nuclei, no cytoplasmic vacuolation or Auer rods and were weakly positive for acid phosphatase and non-specific esterase and negative for PAS, granzyme A, dipeptidyl aminopeptidase IV, ATPase/ADPase and lysozyme production. The blasts were positive for CD1a, CD4, CD16, CD35, HLADR, HLADQ, CD11b, CD11c, CD14, CD33, CD34, CD11a, CD71, CD19, CD25, IL-2R beta and negative for CD2, CD7, CD8, CD10, CD22, CD56, CD57, surface or cytoplasmic CD3, TCR delta and TCR beta, HTLV-1p19 and P-glycoprotein. On liquid culture with or without 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days, the blasts formed aggregates of proliferating and elongating cells on the wall of the flasks with a decline in CD34, numerous dendritic processes appeared on the cells and there was strong positivity for ATPase/ADPase, but no other changes in phenotype. No macrophages were observed, indicating derivation from separate DLCs. Cytogenetic analysis showed chromosomal abnormalities and electron microscopy showed Birbeck granules. Southern blotting of DNA showed rearrangement of one allele for both JH and TCR beta but no HTLV-1 related sequences. Culture supernatants from blasts cultured with or without TPA showed the production of large amounts of IL-8, IL-6, TNF-alpha, MIP-1 alpha, IL-10 and interferon gamma and modest amounts of IL-1 alpha, GM-CSF and stem cell factor. The presence not only of CD1a, HLADR, HLADQ and many other characteristics including Birbeck granules, but also differentiation along the lines of DLC with appearance of dendritic processes on the cells and expression of ATPase/ADPase activity, indicate that the leukemic blasts in our patient represented a leukemic counterpart of normal progenitors of DLC and the leukemia a new entity which could possibly be classified as AML-M8. Lastly, many pro-inflammatory cytokines produced by DLC could contribute to inflammation and IL-10 to immunosuppression.
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PMID:Phenotype, genotype and cytokine production in acute leukemia involving progenitors of dendritic Langerhans' cells. 791 55

We have previously shown that the novel hexapeptide WKYMVm can stimulate bactericidal activity in neutrophils obtained from neutropenic patients treated with chemotherapeutic agents for solid tumors. To extend these observations, we evaluated whether WKYMVm can enhance leukocyte bactericidal activity in patients with acute leukemia (AL). Using blood samples withdrawn from 28 AL patients and 31 healthy controls, we found that, in the absence of exogenous WKYMVm, WKYMVm receptor and bactericidal activity did not differ between patients and controls. Addition of WKYMVm markedly increased the bactericidal activities of these cells in a dose-dependent manner. During induction chemotherapy, there were significant increases in bactericidal activity in the presence and absence of 1nM WKYMVm, with higher bactericidal activities at the time of complete remission than at the time of diagnosis or on day 15. During consolidation chemotherapy, WKYMVm had no effect on bactericidal activities. Patients showed significant increase in the concentrations of TNF alpha, IL-1b, IL-6 and IL-8, but significant decrease in the concentrations of IL-2, IL-4 and IL-12. TNF alpha, IL-1b and IL-6 showed significant negative correlations with bactericidal activities of patient neutrophils at time of diagnosis, and IL-4 showed a significant positive correlation with bactericidal activities. Taken together, these findings indicate that WKYMVm enhances bactericidal activity in patients with AL.
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PMID:Enhanced bactericidal function by WKYMVm in patients with acute leukemia. 1795 Aug 44

What is the role of inflammation in Myeloproliferative Neoplasms? This is currently a topic of much debate. In this review, we will discuss experimental results and basic concepts of inflammatory processes in the pathogenesis of myeloproliferative neoplasms (MPN). So, which are the players involved? First, these are the clonal hematopoietic stem cells (HSC) and their normal stem cell counterparts in the bone marrow (BM), as well as their more mature progeny in the BM and the peripheral blood (PB), including neutrophils, macrophages, erythrocytes, and platelets, but also other cell lineages. Second, these cells produce a plethora of inflammatory cytokines, such as interleukin 6 (IL6), interleukin 8 (IL8), TNF-alpha (TNFa), interferon-alpha (IFNa), and others. Third, these cells and cytokines act in concert with non-hematopoietic cells, including endothelial cells and mesenchymal stromal cells (MSCs). The latter cells, in particular GLI1 positive or leptin receptor (LepR) positive stromal cells, may become activated by the hematopoietic clone to give rise to myofibroblasts, producing excessive fibrosis in the bone marrow (myelofibrosis). Ultimately, the inflammatory and fibrotic circuit involving these three key players may lead to progression of the disease, resulting in BM failure and transformation into acute leukemia, also termed blast crisis. Here, we review the role of these three effectors in the pathogenesis of MPN.
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PMID:Role of inflammation in the biology of myeloproliferative neoplasms. 3250 17