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)

Circulating immune complexes (ClC) were estimated in 78 patients of leukaemias and lymphomas by Clq deviation ELISA and PEG assay. In all leukaemias a significant elevation in ClC was seen at the time of first presentation. While in ALL a decrease occurred on therapy as partial or complete remission was achieved, no such fall was seen in AML or CML-BC when treated. ClC levels were much higher in non-Hodgkins lymphoma than in Hodgkins disease and showed a direct correlation with B symptoms and activity of the disease. The ClC levels were highest in null-ALL followed by those in common ALL and T-ALL. The mean duration of remission in patients of ALL without elevation in ClC was much longer than in those with ClC.
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PMID:Circulating immune complexes in leukaemias and lymphomas. 139 53

The effects of various compounds which modulated the intracellular signal transduction on the induction of class I major histocompatibility complex (MHC) antigens by recombinant human interferon-gamma (rIFN-gamma) were investigated using K562, chronic myelogenous leukemia cells. Class I or class II MHC antigens were not expressed in untreated K562 cells and rIFN-gamma (600 units/ml) weakly induced class I antigens on the cells. Among the compounds tested, verapamil but not the calcium ionophore A23187 enhanced the rIFN-gamma-induced class I antigen expression at both the surface molecule and mRNA levels and enhancement by verapamil occurred in a dose-dependent manner at non-toxic concentrations examined (approximately 50 microM). Verapamil alone had no inducible effect on MHC antigen expression. Deprivation of Ca2+ in culture medium by ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) could not cause an enhancement of class I antigen induction by rIFN-gamma. Simultaneous exposure of K562 cells to rIFN-gamma (600 units/ml) and recombinant human tumor necrosis factor (rTNF; 1000 units/ml) in combination with verapamil (50 microM) resulted in a further increase of class I antigens in the cells. The expressions of c-myc oncogene in K562 cells were not changed when the cells were treated with rIFN-gamma (600 units/ml) or verapamil (50 microM), either alone or in combination. These results indicate that verapamil synergistically interacts with rIFN-gamma on the class I antigen induction in K562 cells irrespective of c-myc gene expression and that class I antigen induction in this cell line may not be relevant to calcium influx triggered by IFN-gamma.
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PMID:Effect of verapamil on the class I major histocompatibility complex antigen expression in K562 chronic myelogenous leukemia cells treated with recombinant human interferon-gamma. 151 24

A patient with chronic myeloid leukemia secreted an antibody to blood group glycosyltransferases after ABO-incompatible bone marrow transplantation (B recipient/O donor). Peripheral B lymphocytes from the recipient were transformed with Epstein-Barr virus, and then fused by polyethylene glycol with mouse myeloma cell line P3-X63/Ag8.653. After the cloning of the hybridoma cells, a cell line which produced human IgM antibody to blood group glycosyltransferases was established. The antibody completely neutralized B transferase activity at low concentration, while a larger amount of immunoglobulins was required to neutralize A transferase activity.
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PMID:Monoclonal antibody to blood group glycosyltransferases, produced by hybrids constructed with Epstein-Barr-virus-transformed B lymphocytes from a patient with ABO-incompatible bone marrow transplant and mouse myeloma cells. 217 79

The K-562 cell line is a culture of human leukemia stem cells originally derived from a patient with chronic myelogenous leukemia in blast crisis. We have subjected such cells, in the log phase of growth, to countercurrent distribution in a charge-sensitive dextran-polyethylene glycol aqueous-phase system, a method that fractionates cells on the basis of subtle differences in their surface properties, and found that: (1) The cell population is heterogeneous since it is composed of cells with different partition ratios. (2) There is a correlation between increasing cell partition ratios and increasing cell electrophoretic mobilities. (3) Cells under different parts of the distribution curve have dissimilar ratios of cells in different parts of the cell cycle, a phenomenon that may, at least partially, be the basis for the subfractionation of these cells. There is a clear tendency for cells in G0 + G1 + early S to decrease and for those in late S + G2 + M to increase with increasing partition ratios. (4) Sialic acid is a major surface charge component of the cells as evidenced by a dramatic drop in their partition ratios after treatment with neuraminidase.
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PMID:Fractionation of K-562 cells on the basis of their surface properties by partitioning in two-polymer aqueous-phase systems. 244 68

The K-562 cell line is a culture of human leukemia stem cells originally derived from a patient with chronic myelogenous leukemia in blast crisis. We have applied a sensitive method capable of detecting subtle differences in charge-associated and noncharge-related cell surface properties between closely related cell populations to K-562 cells from different sources and having different histories. The method consists of isotopically labeling aliquots of each of two cell populations to be compared with 51Cr-chromate and mixing the labeled cells with an excess of unlabeled cells with which they are to be compared. The mixtures are subjected to countercurrent distribution in either a charge-sensitive or a noncharge-sensitive dextran-poly(ethylene glycol) aqueous two-phase system. The distribution curves are analyzed for total cells (in terms of electronic counts) and labeled cells (in terms of cpm). Alterations in relative specific activities through the distribution curves are indicative of differences in surface properties between such cell populations. Using this method we have found surface differences, both charge-associated and noncharge-related, between any two K-562 cell sublines examined. Interestingly, whereas we observed differences among K-562 sublines, we never witnessed a change in surface properties of the respective sublines. The differences among the sublines examined remained unaltered for more than 40 passages in our hands. It thus appears likely that the event(s) leading to an altered K-562 cell surface, detectable by partitioning, does not occur gradually.
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PMID:Detection of surface differences between closely related cell populations by partitioning. Cultured K-562 cell sublines. 246 26

Partitioning behavior of cells in dextran-poly(ethylene glycol) aqueous phase systems is a sensitive reflection of the cells' surface properties. A decrease in partition ratio, in charge-sensitive phases, of a variety of cell lines as a function of culture growth has been reported by a number of investigators. The basis for this phenomenon remains unclear. We have now studied the surface properties of K-562 cells (a human cell line originally derived from a patient with chronic myelogenous leukemia in blast crisis) during suspension culture growth by countercurrent distribution. The mean partition ratio of viable cells remained constant during 220 h of culture (i.e., well into stationary phase). The decrease in mean partition ratio of the cell population as a whole during culture, previously observed and reported by others, is attributed to the lower partition ratio of non-viable cells which increase with time of culture.
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PMID:The partitioning behavior of K-562 cells associated with different stages of culture growth. 347 51

A 3.75% polyethylene glycol -6000 mediated turbidimetric method was used for the estimation of levels of circulating immune complexes (CIC) in sera of normal human subjects and patients with chronic myeloid leukemia (CML). In terms of equivalents of heat-aggregated gamma globulin (eq.HAGG mg/ml serum), the mean levels of CIC were: 5.69 mg/ml (SD 4.78) in 81 normal human subjects; 22.63 mg/ml (SD 9.86) in 52 untreated CML patients; 7.61 mg/ml (SD 5.74) in 54 CML patients in remission; and 21.70 mg/ml (SD 8.15) in 18 CML patients in relapse. High CIC levels, thus, showed a significant association with the pretreatment -- and relapse -- status of the disease (p less than 0.001 and p less than 0.001, respectively). Though the levels decreased during remission, they were still significantly above the mean level in the controls (p less than 0.05). The CIC level-disease status relationship was clearly evident in the serial studies on 19 CML patients who donated serum samples prior to treatment as well as during remission. Two-dimensional electrophoretic analysis of the CIC samples revealed the presence of a polypeptide (mol. wt approx. 37,000 and pI approx. 5.8) in 10 out of 18 CIC samples from the untreated CML patients. Such a moiety was not detected in six CIC samples from normal subjects. The association of this polypeptide with CML gains support from the observation that in 5 CML patients, this moiety was present in the CIC samples obtained prior to treatment but absent in the samples subsequently obtained during remission.
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PMID:Circulating immune complexes in chronic myeloid leukemia: turbidimetric measurement and two-dimensional electrophoretic analysis. 658 May 15

The 37 K protein, earlier found to be present in 3.75% PEG-precipitates from sera of untreated patients with CML, was further characterized. Gel filtration at neutral pH resolved the PEG-precipitate into a non-IgG containing protein peak-I and a IgG containing peak-II. Immunoprecipitation of peak-II with antihuman IgG antiglobulin and subsequent 2D-SDS-PAGE analysis of the immunoprecipitate revealed the presence of 37 K protein in peak-II confirming its association with IgG. 125I-37 K protein was found to interact with antibodies isolated from autologous and allogenic CML-CIC samples but not with similarly isolated antibodies from normal subject, and patients with AML, ALL, MF, and HD. Peptide maps generated by tryptic digestion of 37 K protein (from five different CML patients) were found to be identical. Specific interaction of 37 K protein with the autologous and allogenic antibodies and identity of peptide maps lead to the conclusion that the 37 K protein is a CML-associated antigen appearing in CIC.
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PMID:Circulating immune complexes in chronic myeloid leukemia: studies on 37 K protein antigen. 659 85

Subcellular fractions prepared from human normal granulocytes and leukemic cells from patients with chronic myeloid leukemia (CML), were examined for 7-ethoxycoumarin O-deethylase activity as well as cytochrome P-450 and cytochrome b5 contents. The average 7-ethoxycoumarin O-deethylase activity was found to be significantly increased in all the fractions of CML cells when compared to the corresponding fractions of the normal granulocytes. The CML cells also differed from the normal cells by exhibiting decreased levels of both cytochrome P-450 and cytochrome b5. Examination of the microsomal and cytosolic fractions of both normal granulocytes and CML cells showed distribution of 7-ethoxycoumarin O-deethylase, cytochrome P-450, and cytochrome b5 in both the fractions. Such distribution seems to be unique for human leukocytes. Solubilization of protein in the postmitochondrial (S1) fractions of both the cell types with sodium cholate in the presence of 20% glycerol and further fractionation with 10% polyethylene glycol 6000 (PEG-6000) yielded a partially purified preparation with enriched 7-ethoxycoumarin O-deethylase activity and cytochrome P-450 as well as cytochrome b5 contents.
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PMID:Mixed function oxidase enzymes in human normal granulocytes and chronic myeloid leukemia cells. I. Detection and estimation. 660 23

The hybrid gene BCR-ABL that typifies chronic myeloid leukemia (CML) represents an attractive target for therapy with antisense oligodeoxyribonucleotides (ODN). A central obstacle in the therapeutic application of ODN is their poor cellular uptake. Adding various lipophilic conjugates to the ODN backbone has been reported to improve uptake, and electroporation of target cells has also been shown to enhance intracellular ODN delivery. We have shown that (1) BCR-ABL-directed ODN will specifically decrease the level of BCR-ABL mRNA, provided that cells are first permeabilized with Streptolysin-O (SL-O), and (2) chimeric methylphosphonodiester:phosphodiester ODN directed against 9 bases either side of the BCR-ABL junction are more efficient ODN effectors than structures composed solely of phosphodiester or phosphorothioate linkages. In this study, we compared the efficacy of lipophilic conjugation, SL-O permeabilization and electroporation on the intracellular delivery and molecular effect of BCR-ABL-directed ODN. b2a2- and b3a2-directed chimeric ODN were synthesized either unmodified or with one of the following groups at the 5' end: cholesterol, vitamin E, polyethylene glycol of average molecular weight 2,000 or 5,000, N-octyl-oligo-oxyethylene, or dodecanol. ODN associated with Lipofectin was also studied. Comparison was made in untreated, electroporated, and SL-O permeabilized KYO1 cells. Uptake was examined by fluorescence microscopy and flow cytometry, using ODN structures that were 3' labeled with fluorescein. The effect on target BCR-ABL mRNA expression was analyzed by Northern blotting. Several conjugated structures associated avidly with the cell membrane without achieving significant intracellular uptake or molecular effect. Similarly, ODN:Lipofectin complexes moderately increased cell association, without enhancing intracellular levels of ODN or inducing detectable molecular effect. In SL-O permeabilized or electroporated cells, uptake was approximately 1 to 2 logs greater than in untreated cells, and rapid nuclear localization was seen, especially with unmodified chimeric ODN. In SL-O permeabilized cells treated with ODN directed to the b2a2 and b3a2 junctions respectively, b2a2 BCR-ABL mRNA levels at 4 hours were reduced to 2. 6% +/- 2.1% and 38.4% +/- 1.3% of control values. In cells permeabilized by electroporation, BCR-ABL mRNA levels were decreased to 4.0% +/- 1.4% of control levels by b2a2 directed ODN, although very little nontargeted suppression was seen with b3a2-targeted ODN (93.4% +/- 4.2% of control). Greater cell to cell variation in ODN uptake was seen for SL-O permeabilized cells when compared with electroporated cells, suggesting that, after SL-O permeabilization, relatively unpermeabilized and overpermeabilized populations may coexist. No structure had any effect on the level of irrelevant (p53, MYC, and GADPH) mRNA levels. We conclude that the conjugation of chimeric ODN with one of the above-mentioned lipophilic groups or the complexing of ODN with Liopfectin does not improve either intracellular delivery of ODN or the molecular effect. In contrast, both electroporation and SL-O permeabilization (1) considerably enhanced uptake of chimeric ODN (even for structures without a conjugate group) and (2) achieved significant suppression of target mRNA levels.
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PMID:Improving the intracellular delivery and molecular efficacy of antisense oligonucleotides in chronic myeloid leukemia cells: a comparison of streptolysin-O permeabilization, electroporation, and lipophilic conjugation. 961 72


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