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)

Untreated and retinoic acid (RA) treated human leukemia-lymphoma cell lines reflecting hematopoietic cells at various stages of differentiation, were examined electron microscopically for their surface negative charge distribution using cationized ferritin (CF), an electron dense label of anionic sites. The results indicate that there is a correlation between the CF labeling density/distribution and the stage of lymphoid cell differentiation. Viable unfixed null cell lines show a low CF labeling density with few and small CF patches. A gradual increase in CF labeling density and increase in size and number of CF patches correlates with the stage of differentiation on cell lines of both T or B origin. Treatment of viable unfixed cells with 10(-5) MRA for 10 days seems to prevent the CF-induced formation of CF patches, resulting in a continuous and even distribution of the CF label, similar to that observed on the surface of cells fixed before CF labeling. Some correlation between the distribution of surface anionic sites and the malignant potential of the human leukemic lines could be detected.
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PMID:Distribution and modulation of surface charges of cells from human leukemia-lymphoma lines at various stages of differentiation. 375 71

Serum-free cultures of HL60 promyelocytic leukemia cells and cultured fresh leukemia and normal marrow cells were used to investigate relationships between proliferation, transferrin receptor (TfR) display and intracellular ferritin (Fer). HL60 cells in serum- und Tf-free medium displayed 3 times less TfR than cells in serum or Tf containing medium. But Fer in Tf-independent cells was 50 times higher than Fer in serum- or Tf-supplemented cells. HL60 cells induced to differentiate by DMSO or vitamin D3 decreased TfR but increased Fer. Expression of TfR with fresh leukemia and normal marrow cells was less clear than in HL60 cells; DMSO or vitamin D3 induced differentiation was associated with a 10-fold Fer increase in leukemia cells and greater than 100-fold increase in marrow cells. TfR-expression and ferritin synthesis may be important events in cell differentiation and growth.
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PMID:[Interrelation between transferrin receptor expression and intracellular ferritin concentration in leukemia cells and normal marrow cells]. 378 30

The bone marrow of a patient with acute undifferentiated leukemia developed unique colonies after a 14-day culture in erythropoietin (EPO)-containing methylcellulose. The colonies consisted of 20 to 200 nonhemoglobinized large blast cells. Cytogenetic analysis of single colonies revealed hypotetraploid karyotypes with several marker chromosomes that were identical to those found in directly sampled bone marrow. The concurrently formed erythroid bursts showed only normal karyotypes. No leukemic colony formation was observed in other culture systems with either colony-stimulating activity (CSA) or phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). The leukemic colonies exhibited a complete EPO-dose dependency similar to that of the patient's normal BFU-E. Although cytochemical and immunologic marker studies of the bone marrow cells failed to clarify the cell lineage of the leukemic cells with extraordinarily large cell size, ultrastructural study revealed erythroid differentiation such as siderosome formation in the cytoplasm and ferritin particles in the rhophecytosis invaginations. These findings indicate that the patient had poorly differentiated erythroid leukemia and that some of the clonogenic cells might respond to EPO in vitro. Corresponding to this biological feature, the leukemic cells were markedly decreased in number in response to repeated RBC transfusions, and partial remission was obtained. These observations suggest that erythroid leukemia distinct from erythroleukemia (M6) with a myeloblastic component, can develop as a minor entity of human acute leukemia.
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PMID:Leukemic blast cell colony formation in semisolid culture with erythropoietin: a case report of acute poorly differentiated erythroid leukemia. 380 69

A systematic analysis of the blast cell population was carried out on samples from 50 patients suffering from blast transformation of chronic granulocytic leukaemia (CGL) (31) and of myelofibrosis (4), acute myelofibrosis (AM) (11) and undifferentiated acute leukaemia (4). Transmission electron microscopy (TEM), used in 41 samples, included: morphology and techniques for myeloperoxidase (MPO), platelet-peroxidase (PPO) and acid phosphatase (AP). The majority of cases were also studied by light microscopy cytochemistry and with a battery of cell markers which are reported in the accompanying paper (San Miguel et al, 1985). The characterization of the type(s) of proliferating blasts was made from the integration of ultrastructural and immunological data. TEM morphology allowed the precise recognition of specific granules in basophil and mast-cell precursors and of ferritin particles in blasts of erythroid lineage; these rare cell types were not adequately characterized by other methods. The PPO reaction made possible the identification of pure megakaryoblastic proliferations in 38% of cases, including eight of the 11 with AM; megakaryoblasts were also present in nine of 12 cases with mixed blast cell types. The MPO and AP reactions were useful for the characterization of myeloblasts and monoblasts, respectively. Lymphoblasts could be distinguished from other cell types by TEM morphology and negative MPO and PPO reactions. TEM techniques were valuable for diagnosing correctly the type of blast cell in this study in which only four cases (8%) remained unclassifiable.
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PMID:Characterization of blast cells in chronic granulocytic leukaemia in transformation, acute myelofibrosis and undifferentiated leukaemia. I. Ultrastructural morphology and cytochemistry. 385 50

This report describes two elderly patients with acute leukemia in which blast cells were undifferentiated with conventional light microscopy (L.M.) and cytochemistry. Blast cells were identified as belonging to the erythroblastic line by their ultrastructural features: glycogen deposits, lipidic vacuoles, cytoplasmic ferritin molecules and rhopheocytotic invagination. Moreover, blast cells were surrounding a central macrophage. Thus, these two patients had acute erythroblastic leukemia which differs from erythroleukemia (M6 of FAB classification) in which blast cells present myeloblastic characteristics.
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PMID:Acute erythroblastic leukemia presenting as acute undifferentiated leukemia: a report of two cases with ultrastructural features. 385 11

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

To evaluate whether cerebrospinal fluid (CSF) ferritin could be of diagnostic value in haematological malignancies with central nervous system (CNS) involvement, the ferritin concentration was measured in 21 patients with acute leukaemia and lymphoma. Of the 17 patients without CNS involvement, 16 had CSF ferritin values in the normal range (2-7 micrograms/l); 1 patient had an elevated value, probably due to blood contamination in connection with a very high serum ferritin level. 4 patients had tumour invasion of the CNS indicated by the presence of blastic cells in the CSF; CSF ferritin levels in these patients were likewise in the normal range. There was no difference between CSF ferritin values in patients with and without CNS involvement. With the present assay, measurement of CSF ferritin appears to be irrelevant in the evaluation of CNS invasion in haematological malignancies.
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PMID:Cerebrospinal fluid ferritin in patients with leukaemia and malignant lymphoma. 386 34

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

Acidic isoferritins have been previously found to be highly potent inhibitors of hematopoietic progenitors at concentrations of 10(-16) to 10(-18) mol/L, and it has been suggested that acidic isoferritin inhibitory activity plays a role in the regulation of normal hematopoiesis and also in the pathogenesis of leukemia. To characterize the ferritin species that affect the in vitro growth of human colony-forming unit-granulocyte-macrophage (CFU-GM), we tested different preparations of basic (L-subunit-rich) and acidic (H-subunit-rich) isoferritins. Three preparations of human liver (basic) ferritin did not show any effects on CFU-GM growth at concentrations up to 10(-9) mol/L, irrespective of the degree of glycosylation. Acidic isoferritins were purified both from HeLa cells and human heart. HeLa cell ferritin did not affect in vitro colony formation. One of two preparations of human heart ferritin, containing 5% glycosylated ferritin, showed a mean inhibition of 26% +/- 8% of the control at 10(-9) mol/L (P less than .02), whereas the other preparation, which contained no glycosylated ferritin, did not show any effect of CFU-GM growth. A preparation enriched for glycosylated acidic isoferritins from human heart was found to produce a mean inhibition of 32% +/- 11% of the control at 10(-9) mol/L (P less than .01), whereas another one was ineffective. A significant part of the inhibitory activity was removed by preincubation with the monoclonal antibody 2A4 directed against human heart ferritin. The present findings indicate that basic isoferritins, ie, the predominant ferritin type in human blood, have no effect on the growth of human CFU-GM, and this is in keeping with indirect clinical evidence. Inhibition of colony formation may be obtained by some preparations of acidic isoferritins that are rich in H subunits and bind to concanavalin A. The mechanism(s) responsible for this are not clear, but the effective concentrations are higher than those found in human blood both under normal conditions and in leukemia. At present, the physiologic significance of the observed inhibitory activity is uncertain.
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PMID:Effect of acidic and basic isoferritins on in vitro growth of human granulocyte-monocyte progenitors. 394 47

Two new serological specificities were identified on the surface of murine leukemia virus (MuLV)-infected cells by direct and absorption immunofluorescence tests. Both antigens were detected with antisera prepared in rats that were growing transplants of syngenic MuLV-induced leukemias. Antigen G(L) was defined with the AKR leukemia K36 as the test cell; antigen G(T) was defined with the W/Fu leukemia C58(NT)D as the test cell. G(L) and G(T) antigens were serologically and genetically independent of the MuLV-induced Gross and G(IX) cell-surface antigens. G(L) and G(T) antigens were found in normal lymphoid cells of mice from high-leukemic strains, but not in lymphoid tissues of mice from most low-leukemic strains. Tumors and leukemias of mice of low-leukemic strains often were G(L) and G(T) positive. Similarly, infection of normal cells with MuLV resulted in expression of G(L) and G(T). With ferritin-labeled antibody the G(L) and G(T) antigens were observed on virus-free segments of the cell surface. Genetically, G(L) and G(T) antigens were each controlled by two dominant unlinked genes in AKR mice; these same antigens were each controlled by three or more dominant unlinked genes in C58 mice. Penetrance of G(L) and G(T) regulatory genes was dependent upon the Fv-1 genotype of the host. Expression of G(L) antigen was closely associated with virus production, whereas expression of G(T) antigen was less closely associated.
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PMID:Cell surface antigens associated with murine leukemia virus: definition of the GL and GT antigenic systems. 435 63


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