Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ferritin has a protein shell of 5 X 10(6) Da consisting of 24 subunits of two types, a heavier (H) chain of 21,000 Da and a lighter (L) chain of 19,000 Da. A cDNA clone of the messenger for the L subunit has been isolated from a human monocyte-like leukemia cell line. The clone contains an open reading frame of 522 nucleotides coding for an amino acid sequence matching 97% of the published sequence of human liver ferritin L subunit determined by sequenator, but it corresponds to only 55% of the reported amino acid sequence of a human liver H-subunit clone. Nevertheless, computer analysis of the subunit conformations predicted from the open reading frames of the L and H clones shows that most of the amino acid differences are conservative and would allow both subunits to form the five alpha-helices and beta-turns established by x-ray crystallography for horse spleen ferritin subunits. This suggests that L and H subunits are structurally interchangeable in forming an apoferritin shell. The 5' untranslated region of our human ferritin L clone has considerable homology with that of the rat liver ferritin L clone in the region immediately upstream from the initiator codon, notably showing an identical sequence of 10 nucleotides at the same position in both subunit clones that may participate in regulating the known activation of ferritin mRNA after iron administration. Extensive homology, including several blocks of nucleotides, was identified between the 3' untranslated regions of the human and rat L clones. The common structural features of the H and L subunits lead us to conclude that they have diverged from a single ancestral gene.
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PMID:Structure of human ferritin light subunit messenger RNA: comparison with heavy subunit message and functional implications. 385 10

High serum ferritin levels without any correspondence to the amount of total body storage iron have been found in patients with leukemia. Investigating 96 adults with different types of leukemia, we found that serum ferritin can be used as a tumor marker in myeloid leukemias. Extremely high serum ferritin levels were seen in acute myeloblastic leukemia before treatment and in blastic crisis of chronic myeloid leukemia (ie, 21-fold increased serum ferritin concentrations). Patients with acute myeloblastic leukemia in complete remission had their ferritin concentrations decreased to normal. A relapse of the disease was paralleled by a repeated increase of serum ferritin level. In patients with chronic myeloid leukemia during the chronic phase we found normal serum ferritin concentrations, whereas blast crisis was associated with highly raised serum ferritin levels. We conclude that serum ferritin concentration must be valued as a clinically useful tumor marker in these types of leukemia, exhibiting a helpful and simple parameter in monitoring the activity of the disease.
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PMID:Ferritin--a tumor marker in myeloid leukemia. 386 36

Lactoferrin (LF)--in various quantities--is present in human milk, secretions and polymorphonuclear neutrophils (PMN). LF's significance lies in its bacteriostatic effect on its environment. Probably it prevents bacterial uptake of iron, leads to damage of bacteria and during phagocytosis helps the organism to combat pathogens. Most likely it regulates iron absorption, and during inflammation it takes part in the plasma iron transport. LF is believed to play an important role in the regulation of granulopoiesis in the bone-marrow. From its biological effects it appears that plasma LF determinations may be useful in the clinical diagnosis of leukaemia and other malignant diseases, as well as in the study of iron metabolism.
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PMID:The biological role of lactoferrin. 388 89

Essential thrombocythaemia was diagnosed in a series of 18 patients on the basis of platelet counts greater than 1,000 X 10(9)/1. Radionuclide studies have been carried out to distinguish thrombocythaemia as a primary disease from polycythaemia vera, myelofibrosis and chronic granulocytic leukaemia presenting with high platelet counts. These have included blood volume and spleen function, and radio-iron (52Fe) has been used to demonstrate the presence of extramedullary (splenic) erythropoiesis. The value of these investigations in distinguishing between the various myeloproliferative disorders associated with thrombocythaemia is illustrated.
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PMID:Blood volume, erythrokinetics and spleen function in thrombocythaemia. 393 44

The ability of iron to stimulate the growth of L1210 cells both in DBA-2 mice and in cell culture is evaluated. Although in vitro stimulation is absent, in vivo studies clearly indicate higher numbers of tumor cells in the presence of supplemental iron. When mice were given iron i.p., at levels comparable to clinical doses for humans (24 mg/kg body weight), the tumor load recovered from their peritoneum was substantially greater than from controls without iron supplements. Furthermore, at higher levels of supplemental iron (250 mg Fe/kg body weight), the pretreated animals inoculated with L1210 cells died in 9.7 d whereas controls died in 12.2 d (i.e., 25% faster). As expected, the lower iron dose (24 mg/kg) also resulted in shorter life spans, although the effects were less striking. It is the belief of these authors that these data support the opinion that "anemia of chronic disease" associated with leukemia and possibly other malignancies may represent a host defense mechanism as has been postulated by others (1, 8).
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PMID:Influence of iron on in vivo proliferation and lethality of L1210 cells. 397 48

In a murine model it has been shown that the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132) can be depleted by administration of macrophage (M phi) blockers. In the present study, the role that M phi play in the antitumor activity of the compound was investigated. Oral administration of Ge-132 in mice was demonstrated to be effective in activating M phi (Ge-132-cytotoxic M phi), and the cytotoxic activity of these M phi appeared in the peritoneal cavity of mice 48 hours after the oral administration of the compound. Co-cultivation of RL male-1 leukemia or Ehrlich carcinoma cells with Ge-132-cytotoxic M phi in vitro resulted in marked suppression of the growth of tumor cells. The transfer of peritoneal exudate cells (PEC), or purified M phi fractions of PEC from Ge-132-treated mice to mice bearing Ehrlich or RL male-1 ascites tumors resulted in significant protection. However, when the cytotoxic M phi were depleted by carbonyl-iron treatment in vitro, no antitumor effect was demonstrated in mice bearing Ehrlich or RL male-1 ascites tumors. Macrophage fractions obtained from PEC of Ge-132-treated mice exhibited an inhibitory effect against certain tumors both in vivo and in vitro suggesting that the antitumor effect of Ge-132 observed in vivo resulted from the activation of M phi.
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PMID:[Suppression of tumor growth by peritoneal macrophages isolated from mice treated with carboxyethylgermanium sesquioxide (Ge-132)]. 406 10

Reduced serum concentrations of nutrients like iron, zinc and folates and of albumin and cholesterol are found, as well as emaciation, both in malnutrition and in cancer. In patients with leukemia, a depletion of intracellular potassium and hypo-potassemia are found in addition. The use of hyperalimentation in cancer was originally based on the concept that too little food is the cause of these disturbances in the nutrition state. However, there is also a disturbed metabolism of nutrients in patients with tumors and inflammatory disease. In the case of folic acid, the disturbed metabolism could not be normalized by hyperalimentation. The more advanced the disease, the more pronounced is the disturbed nutrient metabolism, and this disturbance is related to the macrophage activity. It is not self-evident, therefore, that hyperalimentation can normalize the nutritional state in cancer. Emaciation in cancer patients is not caused exclusively by malnutrition.
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PMID:Folate and iron metabolism in patients with tumors and inflammations. 406 5

RNA tumor viruses contain a characteristic RNA-dependent DNA polymerase (reverse transcriptase) which has been thought to be related to the induction of leukemia by this virus. A disturbance in a zinc-dependent enzyme system was first postulated to account for the demonstrated differences in zinc metabolism of normal and leukemic leukocytes [Vallee et al. in (1949) Acta Unio. Int. Contra Cancrum 6, 869 and (1950) Acta Unio. Int. Contra Cancrum 6, 1102]. In order to investigate the relationship between zinc and the initiation of leukemia in chickens by avian myeloblastosis virus, we have examined the metalloenzyme nature of its reverse transcriptase. The present data show that this protein is a zinc metalloenzyme demonstrating the postulated relationship between zinc and a leukemic process. Paucity of purified enzyme generated the design of a novel system of analysis incorporating microwave-induced emission spectrometry combined with gel exclusion chromatography. It provides precision, reproducibility, and remarkable limits of detection on mul samples containing 10(-12) to 10(-14) g-atoms of metal, and is thus orders of magnitude more sensitive than other methods. The chromatographic fraction with highest enzymatic activity contains 1.8 x 10(-11) g-atoms of zinc per 1.6 mug of protein, corresponding to either 1.8 or 2.0 g-atoms of zinc per mole of enzyme for a molecular weight previously determined either as 1.6 or 1.8 x 10(5). Copper, iron and manganese are absent, i.e., at or below the limits of detection, 10(-13) to 10(-14) g-atoms. Agents known to chelate zinc inhibit the enzyme, while their nonchelating isomers do not. The data underline the participation of zinc in nucleic acid metabolism and bear importantly upon the lesions that accompany leukemia and zinc deficiency.
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PMID:RNA-dependent DNA polymerase (reverse transcriptase) from avian myeloblastosis virus: a zinc metalloenzyme. 413 17

Rat leukemia cells IRC 741 in suspension culture form single cytoplasmic protrusions by which the cells preferentially adhere to one another. The induction and/or maintenance of these protrusions is sensitive to changes in intercellular contact, pH, temperature, and nutritional conditions. The protrusions are stable, rigid structures which take part in intercellular adhesion but not in adhesion to substrata. Movement on substrata occurs by means of ruffling membranes formed on the main cell body. This asymmetry in cellular form and function is associated with specialized cell surface regions. Ultrastructurally, the cell surface over the protrusions lacks microvilli, and is covered with a 3,000-4,000-A thick cell coat consisting of 200-500-A electron-dense particles in an amorphous matrix. In contrast, the surface over the main cell body has microvilli and a 200-A wide cell coat which lacks particles. The extracellular particles overlying the protrusions have electron-lucent cores, are protease- and pepsin-resistant, and do not stain with colloidal iron, while the matrix in which they are embedded is sensitive to proteolytic enzymes and contains acidic moieties. The negative surface charge density over the protrusions is higher than that over the main cell body, as shown by the orientation of the cells in an electric field. The unexpected observation that a region of higher charge density is one of increased intercellular adhesiveness might be explained, in part, by the rigidity of the protrusions and by the very small radius of curvature of the overlying extracellular particles. The protrusions permit the observation of discrete regions, differing in charge density, on the surface of living leukemia cells.
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PMID:Structural and functional heterogeneity of the surface of rat leukemia cells. 427 52

The serum ferritin concentration is increased in both acute myeloblastic leukaemia and Hodgkin's disease. In acute leukaemia the mean concentration is about ten times the normal level and is associated with a high concentration of transferrin-bound iron. In Hodgkin's disease abnormal ferritinaemia is associated with a low concentration of transferrin-bound iron and appears to result from a block of reticuloendothelial iron release. Increased concentrations of circulating ferritin have also been observed in a few cases of chronic leukaemia and myelomatosis.
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PMID:Ferritinaemia in leukaemia and Hodgkin's disease. 451 89


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