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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A primary xenogeneic culture system has been devised that selectively generates undifferentiated TdT+ lymphoblasts from rat bone marrow under conditions that do not support the growth or maintenance of rat colony-forming unit-spleen (CFU-S) or granulocyte/macrophage colony-forming cells (GM-CFC). The culture system requires a mouse bone marrow feeder layer, and a serum supplement that has markedly reduced levels of cortisol. The growth of TdT+ cells can be significantly enhanced by the addition of mesodermalizing factors (e.g., fibroblast growth factor, guinea pig bone marrow extract) to the culture medium, and the serum supplement can be decreased by the addition of selenium, transferrin, and T3. The cultured TdT+ cells are antigenically "null" cells that further resemble their normal counterparts in bone marrow with respect to morphology, size, cortisone sensitivity, and pattern of TdT fluorescence. The TdT+ cells are generated with equal facility from bone marrow of normal and congenitally athymic rats, can be maintained in logarithmic growth for at least 10 mos by serial passage in vitro, and do not cause leukemia when infused into irradiated recipients. Although the lineage relationships of these immature lymphoid cells have not yet been established, our working hypothesis, based on preliminary evidence, is that the cultured TdT+ cells are primitive members of the T cell series.
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PMID:A selective culture system for generating terminal deoxynucleotidyl transferase-positive (TdT+) lymphoid precursor cells in vitro. I. Description of the culture system. 621 Mar 37

A murine monoclonal antibody (OKT9) raised against human leukemic cells binds to a wide variety of leukemia and tumor cell lines and to a minority of leukemia cells taken directly from patients. Fetal thymus and liver are strongly reactive as are some normal, immature hemopoietic cells and activated lymphocytes. Reactivity with OKT9 appears to correlate with proliferation status in both normal and malignant populations. Biochemical analysis indicates that this structure is a approximately equal to 180,000-dalton glycoprotein with two disulfide-bonded subunits of approximately equal to 90,000-daltons. Isolation of the transferrin receptor from a T-cell line (MOLT-4) indicates that it also has a dimeric approximately equal to 180,000-dalton structure. Radio-labeled transferrin bound to its receptors can be specifically precipitated by the monoclonal OKT9, although the latter does not bind transferrin itself, indicating that the antigenic structure defined by this antibody is likely to be the transferrin receptor.
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PMID:Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin. 627 Jun 80

The monoclonal antibody OKT9 reacts specifically with the receptors for transferrin on human cells (Sutherland, D. R., Delia, D., Schneider, C., Newman, R. A., Kemshead, J., and Greaves, M. F. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 4515-4519; in Leukemia Markers (Knapp, W., ed) pp. 157-160, Academic Press, New York) and has been used to isolate and characterize this receptor. The receptor is a dimeric glycoprotein (Mr = 180,000) composed of two subunits (Mr = 90,000) and has a pI of approximately 5.2. The transferrin receptor appears to be a transmembrane molecule and is phosphorylated, the phosphate group being predominantly on serine residues. The cell surface form of the molecular possesses both complex and high mannose oligosaccharide chains, which do not appear to have a direct role in antibody (OKT9) binding. The molecule can be cleaved into a Mr = 70,000 fragment from the cell surface, suggesting that the major part of the receptor is exposed to the extracellular environment. The released Mr = 70,000 fragments are not disulfide-linked and possess the antibody (OKT9)- and transferrin-binding sites. Cross-linking studies using radiolabeled transferrin suggest that two molecules of transferrin are bound to each Mr = 180,000 receptor dimer.
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PMID:Structural features of the cell surface receptor for transferrin that is recognized by the monoclonal antibody OKT9. 628 84

Antigens have been detected in 35 to 40% of sera from patients with leukemia that cross-react with the Mr 30,000 core proteins (p30) of baboon endogenous virus (BaEV) and/or of simian sarcoma-simian sarcoma-associated virus (SiSV) in a solid-phase enzyme immunoassay using anti-SiSV p30 and anti-BaEV p30 antisera. These antigens could not be found in sera from nonleukemic persons. Fetal calf serum; normal chicken, goat, rabbit, and rhesus sera; and normal human serum components like albumin, immunoglobulins, and transferrin did not react with the anti-SiSV p30 and anti-BaEV p30 antisera. The reactivity in the leukemic sera was abolished by treatment with protease, but not with glycosidases. The antigens purified by immunoaffinity chromatography showed essentially one band with an apparent molecular weight of 70,000 on sodium dodecyl sulfate: polyacrylamide gel electrophoresis. In competition enzyme-linked immunosorbent assays the leukemia-associated antigens competed out SiSV p30 in the anti-SiSV p30 system. Peptide mapping experiments with antigens from sera of two different leukemic patients showed that the two antigens were identical concerning numbers of peptides and their position. Eleven of 21 major peptides of SiSV p30 and 10 of 20 major peptides of BaEV p30 (50 to 60% of major peptides) showed mobilities identical with those of the major peptides of the human antigens. The data suggest the presence in human sera of retroviral antigens closely associated with leukemia.
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PMID:Detection and biochemical characterization of antigens in human leukemic sera that cross-react with primate C-type viral proteins (Mr 30,000). 629 60

Erythrocyte survival and ferrokinetic studies were adapted to the cat. For 5 clinically healthy 4- to 9-month-old cats, mean 51Cr-labeled erythrocyte survival was 144 hours, and mean plasma 59Fe-labeled transferrin disappearance halftime was 51 minutes. Erythrocyte use of radioiron was rapid and efficient, with 50% to 80% of labeled iron incorporated into the erythron by 100 hours after injection into the cat. Six cats with feline leukemia virus infection were studied. For 2 cats with erythroid aplasia associated with C subgroup of feline leukemia virus, erythrocyte survival times were similar to those determined for the healthy cats, but plasma radioiron disappearance half time and erythrocyte use of radioiron were markedly diminished.
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PMID:Ferrokinetic and erythrocyte survival studies in healthy and anemic cats. 630 16

Serum copper levels of 132 controls and 122 cancer patients (including Hodgkin's disease, lung cancer, breast cancer, leukemia, untreated patients, and patients in progression) were measured using both atomic absorption (AA) and electron paramagnetic resonance (EPR) techniques. The data pairs were compared using linear regression analysis, EPR versus AA, and all the data (controls and cancers) fit a single regression line with a squared correlation coefficient (r2) of 0.80. Comparison of the subpopulations revealed possible small differences, but none great enough to be of diagnostic value for individual patients. Thus, in a number of cases of practical interest, EPR-determined serum copper levels were essentially redundant with respect to AA measurements. Previous reports recommending the use and possible superiority of EPR for serum copper determinations appear not to have compared the EPR and AA techniques adequately or correctly. EPR serum copper measurements may yet provide unique data in these diseases, but a more detailed analysis of the spectral parameters will be required. EPR-determined serum transferrin levels are also reported.
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PMID:Comparison of electron paramagnetic resonance and atomic absorption serum copper measurements in human normal control and cancer patients. 630 84

The effects of three monoclonal antibodies (B3/25, 43/31, and 42/6) reactive with human transferrin (Tf) receptors on growth of normal and malignant myeloid cells were examined using in vitro culture techniques. When added directly to cultures, all three antibodies caused dose-dependent inhibition of normal granulocyte/macrophage progenitor (CFU-GM) growth. Monoclonal antibody 42/6 was by far the most potent of the three, with an ID50 of less than 5 micrograms/ml. Identical effects were seen on CFU-GM from three patients with chronic myelogenous leukemia. Growth of colonies from two myeloid leukemia cells lines (KG-I, HL60) was also inhibited by all three antibodies, and these cells were generally more sensitive than normal CFU-GM. Blast colony-forming cells from three patients with acute non-lymphocytic leukemia were relatively resistant to the antibodies, and CFU-GM from a patient with myeloid metaplasia were resistant (ID50 greater than 50 micrograms/ml) to 42/6. In liquid culture, growth of the leukemic cell lines was inhibited by saturating concentrations of the three antibodies, although in both liquid and colony culture recovery was seen even after exposure to antibody for periods of up to 72 h. Analysis of the cell-cycle status of these cells showed that the antibodies did not cause accumulation of cells in any particular phase of the cell cycle. Addition to cultures of large quantities of human Tf failed to reverse the inhibitory effects of the antibodies. Competitive binding studies on the leukemia cell lines showed that only 42/6 inhibited binding of Tf to its receptor, although all three antibodies inhibited cell growth. Addition of Fe chelate (as ferric nitriloacetic acid, FeNTA) failed to reverse the inhibitory effects of the antibodies on CFU-GM and HL60 cells, but had variable effects on KG-I cell growth. FeNTA fully reversed inhibitory effects of 42/6 on KG-I cells. We conclude that monoclonal antibodies to Tf receptors can inhibit growth of both normal and malignant myeloid cells. Overall, no selectivity for malignant vs normal cells is apparent, although malignant cells from one individual were more sensitive to colony inhibition by 43/31 monoclonal antibody than normal CFU-GM.
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PMID:Effects of anti-transferrin receptor antibodies on growth of normal and malignant myeloid cells. 630 80

Transferrin receptor expression by the human tumour cell lines CCRF-CEM leukaemia and PMC-22B melanoma was studied, measuring the specific binding of fluorescein isothiocyanate (FITC)-labelled transferrin using a fluorescence-activated cell sorter. By measuring the fluorescence of cells stained at subsaturating concentrations of conjugate it was possible to calculate the average numbers of receptors per cell and the binding affinity by Scatchard analysis. These values (1.9 X 10(5) binding sites/cell, KA 1.2 X 10(9) M-1 for CCRF-CEM during exponential growth and 6.9 X 10(4) binding sites/cell, KA 1.4 X 10(-9) M-1 for PMC-22B) are in close agreement with previously published data obtained using radiolabelled transferrin. The present method, however, allowed the transferrin receptor expression of individual cells within a population to be measured and thus it has been possible to test the hypothesis that transferrin receptor is a marker for cycling cells. Frequency-distribution histograms of transferrin receptor showed a wide range of values for both cell lines during exponential growth. When the extreme ranges were sorted and the cells examined for cellular DNA content it was found that those with the highest transferrin receptor expression were enriched with cells in S, G2, and M phases of the cell cycle, whereas those with low transferrin receptor expression were mainly in G1. However, two-parameter-correlated dot plots of transferrin receptor expression versus DNA content showed there was considerable overlap between the ranges of receptor expression for the different cell cycle compartments. Using a stathmokinetic method we have measured the proportion of quiescent cells in fed plateau phase cultures. Transferrin receptor expression was downgraded under these growth conditions but, contrary to expectation, the decline affected the population uniformly, without the emergence of a distinct, transferrin receptor-negative subpopulation corresponding to the increasing proportion of quiescent cells. Thus, although transferrin receptor expression bears some relation to cell cycle phase and reflects the proliferative activity of populations of cells, it is incapable of identifying individual cells which are out of cycle.
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PMID:Transferrin receptor expression during exponential and plateau phase growth of human tumour cells in culture. 631 4

The toxic A chain of ricin was linked to human transferrin via a disulfide bond and the resulting conjugate was shown to bind to cell membrane transferrin receptors. Surface-localized transferrin A chain (TF-A chain) gained access to the cytoplasm and inactivated ribosomes as witnessed by a rapid curtailment of cellular protein synthesis (t1/2 = 6 h) and subsequent cytolysis. The intact conjugate produced potent cytotoxic effects on human leukemia CEM cells, (ID50 = 3 X 10(-11) M), while a 10,000-fold higher concentration of uncoupled transferrin plus A chain was required for comparable action. TF-A chain cytotoxicity was totally blocked by native transferrin or by antibodies directed against ricin A chain and human transferrin. CEM cells gradually acclimated to grow in the presence of TF-A chain displayed 1000-fold resistance to the conjugate while their sensitivity to whole ricin was undiminished. The level of transferrin receptor expressed by these cells was 1/20 the amount present on the parent line and their capacity to bind human transferrin was below the limits of detectability using fluorescent probes. This receptor-deficient cell line was unresponsive to the low levels of transferrin which stimulated proliferation of control CEM cells, but their growth was supported by greatly elevated concentrations of ligand. Receptor variant CEM cells, together with the specific TF-A chain toxin, will be useful for studying the mechanisms for transmembrane delivery of both Fe3+ and ricin A chain into cells and will aid in understanding the growth regulatory functions of the receptor-ligand interaction.
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PMID:A highly cytotoxic human transferrin-ricin A chain conjugate used to select receptor-modified cells. 631 79

Significantly more peripheral blood mononuclear cells (PBM) from 39 patients with lymphoma (p less than 0.001), myeloma (p less than 0.001), or leukemia (p less than 0.001-0.025) bind transferrin (Trf) than those of 23 normals. That Trf was bound to a receptor on these cells was shown by the inhibition of these cells bound to 125I-Trf with unlabeled Trf. The paucity of Trf receptors on PBM from normals and their presence on diseased cells prompt a suggestion that Trf receptors may offer a useful approach to the diagnosis and possible treatment of some blood dyscrasias.
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PMID:Transferrin binding by peripheral blood mononuclear cells in human lymphomas, myelomas and leukemias. 632 90


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