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

Myeloperoxidase (MPO) and elastase, restricted to azurophil granules of neutrophils, as well as lactoferrin, restricted to specific granules of neutrophils, were determined in plasma and serum from patients with acute myeloid leukaemia (AML). Highly sensitive radio immuno assays were developed for detection of these proteins. Serum MPO was increased in 12/35 and decreased in 2/35 patients without correlation to WBC or neutrophil counts; these levels may reflect an abnormal production by leukaemic blasts or ineffective granulopoiesis in the bone marrow. Serum elastase was increased in 6/22 patients. Serum lactoferrin was decreased in 12/25 patients without correlation to neutrophil counts probably reflecting abnormal production. Serum elastase and MPO showed a covariation in chronic myeloid leukaemia but not in AML; the latter finding may indicate that the synthesis of these two proteins is not synchronized in AML-cells. Sequential studies of patients with AML demonstrated fluctuations of serum MPO and lactoferrin during remission most likely because of chemotherapeutic pertubation. Although a limited number of patients has been studied it is suggested that serum lactoferrin may be of help for prediction of relapse in AML.
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PMID:Serum and plasma myeloperoxidase, elastase and lactoferrin content in acute myeloid leukaemia. 22 48

Samples from 49 cases of myeloproliferative diseases were tested by an immunocytochemical technique for leucocyte lysozyme and lactoferrin. The presence of these constituents in myeloid precursors from cases of acute and chronic myeloid leukaemia reflected the degree of cellular maturation, lysozyme appearing (as it does in normal myeloid cells) at the stage of primary granule production (in promyelocytes), while lactoferrin wad detectable only in more mature, secondary granule-containing myeloid cells. Auer rods stained positively for lysozyme, in keeping with their relationship to primary granules. Monocytes from five cases of leukaemia showing predominantly monocytic differentiation were indistinguishable from normal monocytes in their staining reactions for lysozyme despite the presence of raised serum and urinary lysozyme levels. In four cases of acute myeloid leukaemia circulating polymorphs deficient in lactoferrin were detected: in one of these cases a similar percentage of polymorphs was lysozyme negative.
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PMID:Intracellular lysozyme and lactoferrin in myeloproliferative disorders. 32 18

A solid-phase radioimmunoassay is described for measuring lactoferrin levels in normal human plasma. The sensitivity of the assay was 6 ng. per milliliter with an intraassay coefficient of variation of 4 per cent and an interassay value of 9 per cent. Healthy adult males had a mean plasma level of 1.62 mug per milliliter which was significantly higher than adult females, 1.07 mug per milliliter. Postmenopausal females had levels similar to men, 1.74 mug per milliliter, while younger women had a significantly lower mean value, 0.75 mug per milliliter. Two menstruating women and 2 pregnant women had moderately elevated levels. Consistently elevated levels were found in patients with untreated or relapsing chronic myeloid leukemia--all over 12.0 mug per milliliter, while patients on marrow suppressant therapy tended to have subnormal levels. The collection of serum specimens as opposed to plasma, resulted in inconsistently elevated levels: EDTA was the anticoagulant of choice, as heparin interfered in the radioimmunoassay system.
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PMID:A solid-phase radioimmunoassay for the measurement of lactoferrin in human plasma: variations with age, sex, and disease. 106 75

We have previously reported that K562, a chronic myelogenous leukemia cell line, releases a low molecular weight factor (6 to 8 Kd) that inhibits human polymorphonuclear neutrophil (PMN) adherence and adherence-related functions tested in vitro. We now report that this factor, which we have named K562 inhibitory factor (K562-IF), has potent anti-inflammatory activity in mice, associated with an inhibition of PMN functions. Its in vitro actions were less marked with mouse PMN than with human PMN. They included (1) an inhibition of both nonstimulated locomotion and locomotion induced by FMLP or serum; (2) an inhibition of the chemiluminescence induced by opsonized zymosan, but not that induced by phorbol myristate acetate or FMLP; (3) an inhibition of the degranulation stimulated by opsonized zymosan, as reflected by lactoferrin and lysozyme release; and (4) a decrease in arachidonic acid release and leukotriene B4 production by A23187-stimulated PMN. The in vivo actions of K562-IF after intraperitoneal injection included (1) an inhibition of subcutaneous PMN accumulation at the site of injection of opsonized zymosan (PMN accumulated neither outside the vessels nor intravascularly, as shown by means of histochemistry); (2) an inhibition of neutrophil accumulation in the peritoneum of mice having received sodium caseinate or opsonized zymosan intraperitoneally; and (3) lysozyme concentration in neutrophils having reached the peritoneum after opsonized zymosan treatment equal to that in blood, suggesting diminished release. PMN influx and degranulation in the peritoneum were reduced by 50% after 3 hours of treatment with 1 microgram of K562-IF (equivalent to the effect of 120 micrograms of prednisolone). Taken together, these results show that K562-IF is a potent anti-inflammatory agent that acts by inhibiting PMN functions.
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PMID:K562 cells produce an anti-inflammatory factor that inhibits neutrophil functions in vivo. 152 Aug 79

Lactoferrin is a member of the transferrin family of iron-binding proteins. It is found in several glandular epithelial tissues and human neutrophils, where it is localized to secondary granules. To examine the mechanisms controlling lactoferrin gene expression in neutrophils and defects in its expression in acute leukemia, we have cloned a lactoferrin cDNA from a chronic myelogenous leukemia library, and used it to obtain genomic clones representing the chromosomal lactoferrin gene. Using polymerase chain reaction, primer extension, and S1 analysis, we have identified the 5' end of the lactoferrin mRNA. We have defined a putative promoter region for the gene, and characterized its first two exons. In addition, we have examined the structure of these regions in DNA from HL60 cells. HL60 is a leukemic cell line that undergoes phenotypic neutrophil maturation on exposure to dimethyl sulfoxide (DMSO). However, the cells cannot be induced to express any secondary granule protein genes. We have shown that the 5' end of the lactoferrin gene, including the putative promoter region, is entirely normal in HL60. By Northern analysis, nuclear run-on studies, and primer extension assays we have shown that the gene is not transcribed in DMSO-induced HL60 cells. This supports the hypothesis that the defect in HL60 is an abnormality in the production or activity of a transacting regulator of lactoferrin gene expression.
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PMID:Lactoferrin gene promoter: structural integrity and nonexpression in HL60 cells. 158 44

We have isolated and characterized a 2.4-kb cDNA clone encoding human neutrophil collagenase (HNC), a member of the family of matrix metalloproteinases restricted to secondary granules within neutrophils. Partial amino acid sequence was used to deduce oligonucleotide probes. These probes were used to screen a human granulocyte cDNA library derived from messenger RNA (mRNA) from a patient with chronic granulocytic leukemia. Cell-free translation of RNA produced from the cDNA produced a 52-Kd protein that was recognized by anti-HNC antibody. The cDNA clone was sequenced and shown to encode a 467-residue protein whose sequence matched those regions currently known for HNC. The enzyme exhibits 58% homology to human fibroblast collagenase and has the same domain structure. It consists of a 20-residue signal peptide, and an 80-residue propeptide that is lost on autolytic activation by cleavage of an M-L bond. Other regions identified include the autolytic degradation site, the "cysteine switch" residue that is involved in latency and activation, and a putative zinc binding sequence. HNC has six potential N-linked glycosylation sites. The cDNA hybridized to a 3.4-kb mRNA in RNA from a patient with chronic granulocytic leukemia, but not to RNA from uninduced HL60 cells or HL60 cells that had been induced to undergo granulocytic or monocytic maturation with dimethyl sulfoxide or 12-O-tetradecanoylphorbol 13-acetate, respectively. These results parallel those seen with lactoferrin and transcobalamin I, two other secondary granule proteins.
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PMID:Structure and expression of the cDNA encoding human neutrophil collagenase. 164 48

Chronic granulocytic leukemia is a rare myeloproliferative disorder in dogs. The present study investigated various functions of leukemic granulocytes in a dog that presented with thrombocytopenic purpura, anaemia and a classical leukemic hemogram. All analyses were performed in parallel with a control dog. Purification of the leukemic granulocytes by density gradient centrifugation revealed three neutrophil and neutrophil precursor populations with different densities. Comparison of cell morphology and density showed that cell density increased with increasing maturity. The control dog possessed only one neutrophil population, with a density greater than 1.077. Analysis of cellular contents of the granular enzymes, elastase, myeloperoxidase and lysozyme showed that leukemic neutrophils were quantitatively markedly different from normal neutrophils with respect to enzyme activities. There were no major differences between leukemic and normal cells as regards aggregatory and migratory responses to different stimuli. The phagocytic capacity of the leukemic cells, however, was dramatically increased compared with the control, and exceeded all previously encountered responses in the assay employed. In a similar fashion, superoxide generation and secretion of elastase and lysozyme in response to zymosan and phorbol myristate acetate were substantially higher than in the control dog. Priming of cell function to a level exceeding that normally attainable in neutrophils appears to have taken place in peripheral blood of the leukemic dog. The only endogenous mediator known to prime neutrophil functions to the extent seen in the present case is the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which is intimately involved in regulation of myelopoiesis in mammals. On the basis of the enzymological and functional findings in the leukemic dog, we hypothesize that a lactoferrin deficiency in leukemic neutrophils leads to enhanced GM-CSF synthesis, which is ultimately the cause of the observed cellular hyperresponsiveness and contributes to the monocytosis seen in the patient.
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PMID:Enhanced granulocyte function in a case of chronic granulocytic leukemia in a dog. 165 Oct 30

The iron-binding proteins lactoferrin (LF) and H-ferritin have been implicated in the negative regulation of myelopoiesis in vitro and in vivo. The present studies evaluated the functional activity of affinity-purified LF from polymorphonuclear neutrophils (PMN) of patients with chronic myelogenous leukemia (CML) and LF/H-ferritin-cell interactions in a nonleukemic patient with LF deficiency with normal levels of circulating blood leukocytes. Affinity-purified CML-PMN-LF was found to be qualitatively deficient as a suppressor of the release of colony-stimulating factors from mononuclear blood cells, adding to previous information from our group documenting defective LF-cell interactions in CML. LF was detected by immunoradiometric assay in PMN of the patient with LF deficiency, but at a much lower level than normal. This LF was found, however, to be active as a suppressor molecular against the patient's cells and normal donor cells. Patient cells were as responsive as normal cells to effects of purified milk LF. Decreased LF levels in this patient were associated with increased levels of monocyte H-ferritin inhibitory activity, consistent with the known suppressive effects in vitro of LF on H-ferritin release from monocytes. Patient marrow hematopoietic progenitor cells were as responsive as progenitors from normal donors to suppression by purified H-ferritin and prostaglandin E1. These results are consistent with a role of LF and H-ferritin in the control of myelopoiesis in this patient.
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PMID:Qualitative functional deficiency of affinity-purified lactoferrin from neutrophils of patients with chronic myelogenous leukemia, and lactoferrin/H-ferritin-cell interactions in a patient with lactoferrin-deficiency with normal numbers of circulating leukocytes. 204 67

We have examined the ability of bryostatin 1 (bryo), an activator of protein kinase C, to induce differentiation of chronic myelogenous leukemia (CML) cells obtained from peripheral blood. Bryo induced a prompt and persistent macrophage-like differentiation, as evidenced by functional, morphological, and immunological criteria. Differentiated cells remained viable for at least 21 days with little change in cell number. CML cell cultures treated in semisolid medium with bryo showed diffuse infiltration with single macrophages, as well as discrete macrophage, mixed, and granulocytic colonies. Supernatants of suspension cultures of bryo-treated CML cells contained granulocyte-macrophage colony-stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. Furthermore, colony formation could be significantly inhibited by the addition of antibodies to GM-CSF. Prolonged liquid culture of CML cells in bryo reduced colony-forming unit, granulocyte-macrophage content. Bryo-induced differentiation was associated with a decrease in lactoferrin, a marker of granulocyte differentiation, and an increase in both c-fms and interleukin-1 beta RNA, both of which are expressed by monocytes/macrophages. These data demonstrate that bryostatin 1 is capable of inducing macrophage-like differentiation in maturing CML cells. Furthermore, bryostatin induces secretion of GM-CSF by such cells in suspension and semisolid medium and also promotes clonal extinction of granulocyte-macrophage progenitors. Bryostatin may be a possible therapeutic agent for CML.
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PMID:Differentiation and growth modulation of chronic myelogenous leukemia cells by bryostatin. 238 56

In this study immuno-electron microscopy was used to assay, semi-quantitatively, the granule contents of elastase, lactoferrin, lysozyme and myeloperoxidase in human peripheral blood neutrophils from 13 chronic myeloid leukaemia patients in the chronic phase of the disease and from normal non-smoking donors. The fixation conditions that adequately preserved the antibody binding capacities of these antigens and reasonably preserved the ultrastructure of the neutrophils were selected by light-microscopic immunoperoxidase cytochemistry on cytospin smears. Immunogold cytochemistry on LR White resin sections localised elastase and myeloperoxidase to the primary granules, lactoferrin to the secondary granules and lysozyme to both types of granule. When applicable, peroxidase cytochemistry was combined with immunogold staining making it easier to distinguish the primary from the secondary granules. A comparison of the immunolabelling density values obtained for the leukaemic and normal states revealed no significant abnormalities in the immunoreactivity patterns for any of these neutrophil granule antigens in the leukaemic patients. All 13 patients gave normal immunostaining reactivities for these neutrophil granule proteins. Consequently the distribution patterns of these proteins, as shown in this study, cannot be used as indices in distinguishing chronic myeloid leukaemic neutrophils from normal neutrophils.
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PMID:Analysis of human neutrophil granule protein composition in chronic myeloid leukaemia by immuno-electron microscopy. 255 61


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