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)

We previously developed a technique to isolate subchromatin nucleoprotein complexes (NPC) that contain tightly bound genes and enzymatic activities. NPC fractions (NPCF) were prepared by directly treating isolated nuclei with MspI to generate six NPCF (S1, M1, S2, M2, 0.1K and R). The NPCF have been used to predict the potential efficacy of interferon-alpha (IFN-alpha) treatment in patients with chronic myelogenous leukemia (CML) [Nicolson et al., Gene 159 (1995) 105-111]. Here the NPCF were probed for the presence of tightly bound c-abl, p53 and bcl-2 genes. We found that the NPCF isolated from the nuclei of leukocytes of normal individuals rarely contained detectable quantities of tightly-bound c-abl, p53 or blc-2 genes or gene sequences, whereas in CML nuclei these genes were often found in tight association with multiple NPCF. Examination of NPCF isolated from the leukocyte nuclei from patients with highly progressive CML for the presence of the three genes revealed that more NPCF contained the three tightly-bound genes than leukocyte NPCF from patients with stable or less progressed CML. These data suggest that as CML progresses to more malignant states, oncogenes, suppressor genes and apoptosis-associated genes become tightly associated with NPCF.
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PMID:Chromatin nucleoprotein complexes containing tightly bound c-abl, p53 and bcl-2 gene sequences: correlation with progression of chronic myelogenous leukemia. 864 42

Chronic myelogenous leukemia (CML) has a progressive course but little is known about the biologic characteristics of disease progression. This study was designed to assess the changes in cell proliferative characteristics, apoptosis, the expression of the bcl-2 and c-myc genes between the time of initial diagnosis and entrance into the blastic phase of the disease. We observed that the rate of cell proliferation decreased and the cell death rate did not significantly change as the disease accelerated. The level of bcl-2 expression was significantly higher in accelerated/blastic phase cells than in the chronic phase cells in the population as a whole, however, the bcl-2 expression level did not change in blast cell subpopulation. c-myc Expression was significantly higher in the blast cell subpopulation of accelerated/blastic phase than in that of earlier phases of the disease. In conclusion, the characteristics of CML cells, namely proliferation rate, c-myc and bcl-2 change during the course of the disease. It is possible that the change in c-myc expression plays a causative role in evolution of the blastic phase from the chronic phase.
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PMID:Bcl-2 and c-myc expression, cell cycle kinetics and apoptosis during the progression of chronic myelogenous leukemia from diagnosis to blastic phase. 927 59

The selective and conspicuous absence of a novel receptor-Ck (having affinity for cholesterol moiety in lipoproteins and intrinsic tyrosine kinase activity) in various leukemic cell lines/patients, prompted us to explore the nature of interrelationship between receptor-Ck deficiency and over-expression of genes coding for bcl-2, cyclin 'D', chimeric bcr-abl, c-myc and LDL-receptor in the human promyelocytic leukemic cell line (HL-60). This study revealed unambiguously that deregulated expression of these genes is primarily due to the inability of these cells to express the receptor-Ck gene. Based upon the observations we propose that 'receptor-Ck' deficiency may be responsible for the initiation of chronic myeloid leukemia.
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PMID:Receptor-Ck-dependent regulation of genes in HL-60 cell line. 944 38

The effects of the administration of a 3-day course of 13-cis retinoic acid in combination with interferon a [RA/IFN] on the leukemia cells was measured in vivo in 43 patients with chronic myelogenous leukemia. The administration of RA/IFN was associated with a significant fall in the white blood cell count of patients with chronic-phase disease and with a fall in the percentage S-phase cells in CML patients regardless of the stage of their leukemia. In two thirds of the patients studied the administration of RA/IFN was also associated with an increase in marrow apoptosis. The cytokine combination also suppressed bcl-2 and myc expression in a minority of patients and such expression appears to be associated with response to a treatment regimen which includes RA/IFN. These studies are the first to directly assess the effects of the combination of RA/IFN on chronic myelogenous leukemia cells in vivo in patients. These effects, if seen in other malignant diseases, could account for the therapeutic benefit which has been associated with the administration of this combination of biological agents to patients with malignant disease.
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PMID:The effects of 13-cis retinoic acid and interferon-alpha in chronic myelogenous leukemia cells in vivo in patients. 944 43

Effect of low-density lipoprotein (LDL) on the expression of Bcl-2 as well as cyclin 'D' genes was studied in Receptor 'Ck' (+ve) and Receptor 'Ck'(-ve) human lymphocytes. LDL had no effect upon the elevated levels of Bcl-2 and cyclin 'D' gene products in Receptor 'Ck' (-ve) lymphocytes (from untreated CML patients), whereas in Receptor 'Ck' (+ve) lymphocytes (from normal subjects), the exposure to LDL regulated the level of cyclin 'D' gene product without initiating the expression of bcl-2 gene product. However, blockage of Receptor 'Ck' in normal lymphocytes, through its specific antibody (Ab-RCk) in presence or absence of LDL, resulted in the induction of both cyclin 'D' (at 4 h interval) and bcl-2 (at 12 h interval) gene products. Based upon these results, we propose that Receptor 'Ck' deficiency in cells may inherit defective apoptosis and capacity proliferation leading to leukemic transformation.
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PMID:LDL-dependent regulation of Bcl-2 and cyclin 'D' gene expression in lymphocytes from normal and CML patients. 957 Mar 62

We used synthetic RNA transcripts to prove the cleavage capability of ribozymes targeted against bcl-2-related RNAs. No cleavage occurred when control oligonucliotides were used. To assess the functional role of the specific ribozymes in chronic myelogenous leukemia (CML) cell lines we cultured K562, BV173, and Daudi cells for 48 h after lipofection with 10 microM oligonucleotide. An increase in apoptotic cells, dependent on ribozyme specificity, was shown in BV173 cells. This finding was underlined by the typical morphological changes, but there is no correlation with regard to the level of bcl-2 protein expressed. Though bcl-2 appears to interfere with cell death in myeloid cells, bcl-2-targeted ribozymes do not induce programmed cell death (PCD) by reducing bcl-2 protein levels, but rather by a presently unknown mechanism.
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PMID:Bcl-2 mRNA-targeted ribozymes: effects on programmed cell death in chronic myelogenous leukemia cell lines. 961 28

Downregulation of bcr-abl expression in the chronic myelogenous leukemia cell line K562 using antisense oligonucleotides has been shown to enhance the sensitivity of the cells to apoptotic stimuli, suggesting that p210 bcr-abl, like bcl-2 functions as an anti-apoptosis factor (McGahon A et al, Blood 1994, 83: 1179). In these experiments, the inhibition of p210 bcr-abl expression alone was not sufficient to induce apoptosis. We demonstrated that exposure to low doses (0.5 mM) of a butyric acid analog, arginine butyrate, was capable of inducing apoptosis in selected leukemia cell lines, including K562 cells, and in fresh leukemia cells from patients with chronic myelogenous leukemia. To further explore the mechanisms of this effect, we examined expression of p210 bcr-abl after butyrate exposure and found a dose-related inhibition of p210 bcr-abl protein without concordant change in other phosphoproteins, including the JAK-1 kinase. Further analysis revealed that the inhibition of bcr-abl expression occurs due to transcriptional regulation of the bcr-abl gene by arginine butyrate. These results suggest that arginine butyrate and other butyrate analogs alone or in combination may be useful in the therapy of patients with chronic myelogenous leukemia or bcr-abl expressing acute leukemias.
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PMID:Arginine butyrate downregulates p210 bcr-abl expression and induces apoptosis in chronic myelogenous leukemia cells. 963 22

Drug resistance is a common cause of treatment failure in oncology. In addition to the resistance caused by over-expression of p-glycoprotein and similar molecules other mechanisms are involved in the selection or induction of drug resistant tumor cells. In this study, we characterized a CML cell line made resistant to cyclophosphamide (KBM7-B5-1803) further for the expression of apoptosis promoting and inhibiting molecules. We found that KBM7-B5-1803 has a 3 4-fold over-expression of the receptor CD95 (Fas/Apo-1) compared with the parent line. The regulation of CD95 by cytokines was comparable to other types of cells. Despite the inducibility and over-expression of CD95, CD95 failed to trigger apoptosis in both the parent and the drug resistant line. The drug resistant line has a particular pattern of the expression of bcl-2 family members: bcl-2 protein and message were expressed to a similar extent, however, compared with the parent line, the message for bclx short was decreased. P-glycoprotein was not expressed in either cell line. Taken together we show here in a leukemia cell line that the phenotype of cyclophosphamide resistance is associated with a particular pattern of apoptosis-related molecules.
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PMID:Further characterization of cyclophosphamide resistance: expression of CD95 and of bcl-2 in a CML cell line. 978 11

The efficacy of taxanes on human leukemia cells is the object of intensive in vitro investigation concerning the influence of cell-type-specific characteristics on cytotoxic response to drugs. The present study dissects the response to taxanes of HL60 acute myelomonocytic leukemia and of K562 chronic myelogenous leukemia, in parallel over a 72-hr time-span. The kinetics of cytotoxicity following pulsed and continuous exposure to either taxol or taxotere showed a delayed response of K562 cells independently of dose and type of exposure. In K562 cells, apoptosis became evident at 48 hr and prominent at 72 hr of treatment. These events were mirrored by delayed kinetics of caspase-3 activation. Comparable microtubule targeting was demonstrated in HL60 and in K562 cell lines, as bcl-2 and raf-1 were phosphorylated following treatment with taxanes. These observations indicate that early activation processes were responsible for apoptosis, but that the delay was determined by other factors. In addition, cell-free-system experiments excluded the presence of excess nuclear and/or cytoplasmic inhibitory factors and demonstrated that K562 cells possess a fully competent caspase system which can be readily activated. Processing of caspase-3 pro-enzyme was in fact increased by addition of cytochrome c. These results extend to taxol and taxotere the notion that drug-induced apoptosis is delayed upstream of caspase-3 activation in K562 cells, that such kinetics is independent of drug concentration and exposure time, and that it is linked to intrinsic cellular characteristics mapping between bcl-2 phosphorylation and cytochrome c release.
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PMID:Late apoptotic effects of taxanes on K562 erythroleukemia cells: apoptosis is delayed upstream of caspase-3 activation. 1069 26

Molecular diagnostic tests are widely performed in managing hematologic malignancies such as leukemia and lymphoma. In this article, we review the present application and problems of the tests. Karyotyping is performed at diagnosis of all kinds of hematologic malignancies. This method needs dividing cells as samples and skilled experts. Fluorescence in situ hybridization(FISH) analysis using cells in interphase is performed, for example, to monitor the effect of interferon on chronic myelogenous leukemia patients. The weak point of this method is that approximately 2% of false-positive cells are inevitable. Southern blot method is used for clonal analysis in some disease, for example, adult T-cell leukemia/lymphoma. Polymerase chain reaction(PCR) method using genomic DNA is performed for limited types of diseases such as lymphoma with bcl-2/IgH fusion gene. Reverse transcription(RT)-PCR method can detect fusion gene transcripts with high sensitivity. This method is useful for detecting minimal residual diseases after chemotherapy or bone marrow transplantation. To perform quantitative analysis, real-time PCR or competitive PCR must be done. In the near future, new technology such as gene expression profiling analysis using DNA microarrays or spectral karyotyping(SKY) method will be used in clinical practice.
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PMID:[Molecular diagnostic tests in hematologic diseases]. 1130 16


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