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

The cellular origin of the K 562 cell line, established from a patient in the blast crisis of chronic myeloid leukemia has been investigated. In agreement with previous reports, an erythroid differentiation was observed. A minority of immature, but hemoglobinized erythroblasts were identified both by electron microscopy and by immunofluorescence using an antibody to gamma-globin chains. Embryonic and fetal hemoglobin (Hb) were synthesized. Hemin increased the number of erythroblasts as well as the absolute amount of Hb synthesized: the Hb pattern was also significantly modified. By cytochemical ultrastructural detection of peroxidase activity (PA), a weak PA, distinct from granulocytic peroxidases, was found exclusively in the nuclear envelope and rough endoplasmic reticulum in a small number proportion of cells. In its localization this PA resembled that of normal and leukemic promegakaryoblasts. The addition of sodium butyrate or dimethylformamide markedly increased the number of these cells (up to 30%) but did not modify their cytoplasmic maturation. No modification of Hb synthesis was observed. Cloning of the K 562 line revealed a marked heterogeneity from one clone to another in Hb production, in the phenotype of Hb synthesis, and in the inducibility by butyrate or dimethylformamide. An inverse relationship between the number of cells with PA and Hb production was found in the different clones. Recloning some of these primary clones resulted in secondary clones, which displayed properties similar to those from which they had originated. All attempts to obtain granulocytic differentiation by addition of different inducers failed. These results clearly indicate that the K 562 cell line arises from the proliferation of bipotent stem cells, these cells possessing variable capacities of differentiation toward erythroid and presumably megakaryocytic cell lineages.
 ...
PMID:Heterogeneity in the cellular commitment of a human leukemic cell line: K 562. 694 84

Acidic isoferritins have been identified as leukemia-associated inhibitory activity (LIA), which suppresses colony and cluster formation of colony-forming unit-granulocyte macrophages from normal donors but not from patients with leukemia. LIA was detected in all ferritin preparations tested, including ferritin isolated from normal heart, spleen, liver, and placental tissues, and from the spleens of patients with chronic myelogenous leukemia and Hodgkin's disease. Purified preparations of LIA were composed almost entirely of acidic isoferritins, as determined by immunoassay, radioimmunoassay, and isoelectric focusing. The inhibitory activity in the LIA and ferritin samples was inactivated by a battery of antisera specific for ferritin, including those prepared against acidic isoferritins from normal heart and spleen tissues from patients with Hodgkin's disease, and those previously absorbed with basic isoferritins. Antisera absorbed with acidic isoferritins did not inactivate the inhibitory activity. Separation of LIA and chronic myelogenous leukemia and normal spleen ferritin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing confirmed that the regions of peak inhibitory activity corresponded in each to an apparent molecular weight of approximately 550,000 and to a pI value of 4.7. Similar physicochemical characteristics included inactivation by methods that dissociate ferritin molecules into subunits and by treatment with trypsin, chymotrypsin, pronase, and periodate. The purified preparations were extremely stable to heat treatment. The glycoprotein nature of the inhibitory activity was substantiated because it bound to concanavalin A-Sepharose and was eluted off by alpha-methyl mannose. Inhibitory activity of the activity of the acidic isoferritins was detected at concentrations as low as 10(-17)-10(-19) M and iron saturation did not appear to be necessary for its action. These results implicate acidic isoferritins in the regulation of normal myelopoiesis and suggest a role for them in the progression of leukemia.
 ...
PMID:Identification of leukemia-associated inhibitory activity as acidic isoferritins. A regulatory role for acidic isoferritins in the production of granulocytes and macrophages. 697 99

Various chemicals which are known to have positive effects on differentiation of some erythroid cell lines were tested on a human chronic myelogenous leukemia cell line, KU-812F. Succinic acid, 5-azacytidine, daunomycin, and hemin showed a positive effect. Among them, hemin and 5-azacytidine were the most effective inducers for erythroid differentiation of KU-812F cells. Dimethylsulfoxide, cytosine arabinofuranoside, and sodium n-butyrate showed no effect. In addition, subclone KU-812F/33 derived from the KU-812F cell line showed differential expression of the beta- and gamma-globin genes in the presence of either 2 microM 5-azacytidine or 40 microM hemin. Hemoglobin synthesis in differentiated KU-812F/33 cells was analyzed by isoelectric focusing gel electrophoresis, and S1 mapping analysis of beta- and gamma-globin mRNA was performed. After treatment with 5-azacytidine, the beta-globin gene expression was predominantly enhanced (18.75-fold higher level of beta-globin mRNA). After treatment with hemin, the most notable increase was in the gamma-globin gene expression (1.83-fold higher level of gamma-globin mRNA), while no increment of beta-globin was observed.
 ...
PMID:Differential induction of adult and fetal globin gene expression in the human CML cell subline KU-812F/33. 752 36

Perlecan is a modular heparan sulfate proteoglycan that harbors five domains with homology to the low density lipoprotein receptor, epidermal growth factor, laminin and neural cell adhesion molecule. Using a monoclonal antibody directed against the laminin-like domain of perlecan, we have recently shown that perlecan is widely expressed in all lymphoreticular systems. To investigate further this observation we have studied the expression of perlecan in two human leukemic cell lines. Using reverse transcriptase-PCR, ribonuclease protection assay, and metabolic labeling we detected significant perlecan expression in the multipotential cell line K562, originally derived from a patient with chronic myelogenous leukemia. In contrast, the promyelocytic cell line HL-60 expressed perlecan at barely detectable levels. These results were intriguing because the K562 cells do not assemble or produce a classical basement membrane. Following induction with either sodium butyrate or the phorbol diester 12-0-tetradecanoylphorbol-13-acetate (TPA), K562 and HL-60 differentiate into early progenitor cells with erythroid or megakaryocytic properties, respectively. Following treatment of K562 and HL-60 cells with either of these agents, perlecan expression was markedly increased in K562 cells. In contrast, we could detect perlecan protein synthesis in HL-60 cells only at very low levels, even after induction with TPA or sodium butyrate. Collectively, these results indicate that perlecan is actively synthesized by bone marrow derived cells and suggest that this proteoglycan may play a role in hematopoietic cell differentiation.
 ...
PMID:The proteoglycan perlecan is expressed in the erythroleukemia cell line K562 and is upregulated by sodium butyrate and phorbol ester. 754 67

The proteolytic modification of plasminogen activator inhibitor 2 (PAI-2) was studied during apoptosis in the human promyelocytic leukaemic NB4 cell line during treatment with the phosphatase inhibitors okadaic acid and calyculin A as well as the protein synthesis inhibitor cycloheximide. The apoptic type of cell death was ascertained by morphological and biochemical criteria. In cell homogenates PAI-2 was probed by [125I]urokinase plasminogen activator (uPA) and detected as a sodium dodecyl sulphate-stable M(r) 80,000 complex after reducing sodium dodecyl sulphate-polyacrylamide gel electrophoresis and autoradiography. During apoptosis a smaller (M(r) 70,000) uPA-PAI-2 complex was consistently detected. The modification was in the PAI-2 moiety, as the [125I]uPA tracer could be extracted in its intact form from the complex. Thus the cleaved PAI-2 isoform is a biochemical marker of apoptosis in the promyelocytic NB4 cell line. The modified PAI-2 isoform was also detected in homogenates made from purified human mononuclear leukaemic cells aspirated from the bone marrow of patients suffering from acute and chronic myeloid leukaemia.
 ...
PMID:Cleaved intracellular plasminogen activator inhibitor 2 in human myeloleukaemia cells is a marker of apoptosis. 794 88

CAMAL (common antigen of myelogenous acute leukemia) is an antigenic preparation isolated in this laboratory from the bone marrow or peripheral blood leucocytes of persons with myeloid leukemias. Material from CAMAL preparations, which migrates in the range of 30 to 35 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE, P30-35 CAMAL), was shown to exert an inhibitory effect on in vitro colony formation by progenitor cells from normal healthy donors. The same preparations of P30-35 CAMAL, in contrast, exerted a stimulatory effect on in vitro colony formation by progenitor cells from patients with chronic myelogenous leukemia (CML). We now report that both the inhibitory effect on normal colony formation and the stimulatory effect on CML colony formation mediated by P30-35 CAMAL were blocked using phenyl methyl sulfonyl fluoride (PMSF), an inhibitor of the activity of serine proteases. Similarly, both the P30-35 CAMAL-mediated inhibitory effect on normal colony formation and the P30-35 CAMAL-mediated stimulatory effect on CML colony formation were blocked using the peptide ala-pro-phe-CMK, also an inhibitor of serine protease activity. These results suggest the involvement of proteolytic activity, either directly or indirectly, in the alterations of in vitro myelopoiesis exerted by P30-35 CAMAL.
 ...
PMID:Reversal of CAMAL-mediated alterations of normal and leukemic in vitro myelopoiesis using inhibitors of proteolytic activity. 815 56

Intact nuclei derived from murine metastatic large-cell lymphoma and human chronic myelogenous leukemia cells were digested to discrete subchromatin deoxyribonucleoprotein/ribonucleoprotein precursor complexes by treatment with Msp-I. The resultant complexes were composed of nucleoproteins (NPs) that were isolated and purified by two-dimensional isoelectric focusing/sodium dodecylsulfate polyacrylamide gel electrophoresis (2D-SDS-PAGE), electroelution from the gel, and removal of SDS by extractigel chromatography. Various NPs purified by 2D-SDS-PAGE were examined for the presence of oncogenes and tissue-specific genes using a dot-blot hybridization technique. The RNA polymerase products of NPs were labeled, purified, and subsequently used in a back-hybridization assay to identify transcripts for particular genes. By utilizing a 2D-SDS-PAGE Southwestern technique in parallel with the dot-blot and RNA back-hybridization assays, we assessed whether it is possible to "track" a gene and its associations in particular NPs. In patients with chronic myelogenous leukemia, we screened approximately 1000 NPs for bcl-2 sequences and found them present in a single NP of apparent M(r) approximately 19,000, pI approximately 5.5. In murine RAW117-H10 cells transformed by the abl oncogene, we found by Western analysis that an antigen cross-reacting with abl antigen was localized to a p53 gene-containing NP of apparent M(r) approximately 22,000, pI approximately 7.2. A coincident Southwestern experiment using the same blot showed that the abl gene was bound by the same NP. The techniques described present the basis for "tracking" a particular gene to individual NPs and studying its relationship to other genes, their respective gene products, and its binding properties with particular NPs.
 ...
PMID:Nucleoprotein complexes from metastatic cells containing oncogenes and tissue-specific genes: a novel method to track genes associated with specific nucleoproteins. 816 4

CAMAL (common antigen in myelogenous acute leukemia) is an antigenic preparation isolated in this laboratory from the bone marrow or peripheral blood cells of persons with myeloid leukemias and shown in an immunoperoxidase slide test to be diagnostic of these leukemias. CAMAL has been shown to be inhibitory to myelopoiesis by normal progenitor cells in vitro. This activity is associated with material which was further purified from CAMAL preparations, and which migrates at 30-35 kDa by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). We now report that material from CAMAL preparations highly enriched for this 30-35 kDa material is stimulatory to in vitro colony formation by progenitor cells from patients with chronic myelogenous leukemia (CML). This stimulatory effect on CML colony formation was observed to be consistent. Colony formation was stimulated in a biphasic fashion; enhancement was seen at low (1 to 10 ng/ml) and high (100 to 200 ng/ml) concentrations of P30-35 CAMAL, but enhancement was reduced or absent at an intermediate concentration of P30-35 CAMAL (10 to 70 ng/ml), and was not observed at P30-35 CAMAL levels above 200 ng/ml, or below 1 ng/ml. The colony types in cultures of CML clinical specimens targetted for enhancement by P30-35 CAMAL were identified. At low concentrations of P30-35 CAMAL primitive colonies were increased, whereas at high concentrations of P30-35 CAMAL, an increase in all colony types was observed. In addition, an increase in the size of some colonies within P30-35 CAMAL-treated cultures was frequently observed. Colony formation by two cell lines derived from the leucocytes of a patient with CML was enhanced by treatment with P30-35 CAMAL in a manner similar to the stimulation observed using primary cells from CML clinical specimens.
 ...
PMID:Stimulation of leukemic myelopoiesis by P30-35 CAMAL, an inhibitor of normal myelopoiesis. 837 90

The presence and functional role of the cyclic nucleotide signal transduction system was investigated in platelets from patients with myeloproliferative disorders. Platelets from certain patients with chronic myelocytic leukemia showed decreased expression of cGMP-dependent protein kinase, and platelets from two such patients were studied in some detail. These platelets had very little if any cGMP-dependent protein kinase but a normal level of cAMP-dependent protein kinase. They also contained a normal level of VASP (vasodilator-stimulated phosphoprotein, a specific substrate of both cAMP- and cGMP-dependent protein kinase), as well as a functionally intact prostaglandin E1-stimulated cAMP-mediated VASP phosphorylation. In contrast, sodium nitroprusside-stimulated VASP phosphorylation was severely impaired in these cGMP-dependent protein kinase-deficient platelets, despite an exaggerated cGMP response to sodium nitroprusside. Furthermore, whereas selective activation of the cGMP-dependent protein kinase by 8-(4-chlorophenylthio)-cGMP strongly inhibited the ADP- or thrombin-evoked calcium mobilization from intracellular stores in normal platelets, this agonist-evoked calcium response was not inhibited by the cGMP analog in cGMP-dependent protein kinase-deficient platelets. The results demonstrate a defect in the nitrovasodilator-/cGMP-regulated signal transduction system in human platelets from some patients with myeloproliferative disorders, and underscore that a cGMP-dependent protein kinase regulatory system, distinct from that of cAMP-dependent protein kinase or other cGMP-dependent effectors is operative in normal human platelets.
 ...
PMID:Defective nitrovasodilator-stimulated protein phosphorylation and calcium regulation in cGMP-dependent protein kinase-deficient human platelets of chronic myelocytic leukemia. 839 Apr 66

Six patients with thrombotic microangiopathy associated with drug therapy had serial analyses of von Willebrand factor (vWF) multimeric patterns in their EDTA-plasma samples by sodium dodecyl sulfate-1% agarose gel electrophoresis and autoradiography. In the plasma of five patients (one with chronic myelogenous leukemia, two with prostatic cancer, and two with lymphoma), vWF abnormalities were observed during evolution of the thrombotic microangiopathy. These abnormalities were either the presence of unusually large (UL)vWF multimers of the type similar to those found within, and released or secreted by, endothelial cells (three patients) or a relative decrease in the largest plasma vWF multimers of the type that can be induced to attach to platelets (one patient) or both vWF abnormalities in different serial samples (one patient). In the one cardiac transplant patient who did not develop vWF multimeric abnormalities associated with thrombotic microangiopathy, vWF antigen levels were elevated more than threefold. This later individual received therapy with cyclosporin A alone. The other five thrombotic microangiopathy patients received cyclosporin A in combination with other chemotherapeutic agents (two patients); mitomycin-C, along with other chemotherapy (two patients); or multiple chemotherapeutic drugs, but not cyclosporin A or mitomycin C (one patient). The finding of vWF multimeric abnormalities during serial analysis of plasma samples from five of six patients with drug-associated thrombotic microangiopathy suggests the possibility that ULvWF forms derived from damaged or stimulated endothelial cells, along with the largest plasma vWF multimers, may be involved in the intravascular platelet clumping that is an essential part of the pathophysiology of this disorder.
 ...
PMID:Abnormalities of von Willebrand factor multimers in drug-associated thrombotic microangiopathies. 843


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>