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)

The CD11b/CD18 leukocyte integrin molecule mediates diverse neutrophil adherence-related functions, including cell:cell and cell:extracellular matrix attachments. To study the individual role of this leukocyte integrin in cell adherence in hematopoietic cells, we expressed the CD11b/CD18 complex on the surface of K562 cells, a cell line derived from an individual with chronic myelogenous leukemia in blast crisis. We used an amphotrophic retroviral vector designated LCD18SN, harboring the complete coding sequence for the CD18 subunit, to transfer the CD18 cDNA into K562 cells and select stable cell lines. The CD11b subunit in the expression plasmid pREP4 was transfected into these K562/CD18 cells by electroporation and stable cell clones were selected. These K562 cells possessed RNA and intracellular protein for each subunit, and they expressed the CD11b/CD18 heterodimer on the cell surface. When CD11b/CD18 expressing K562 cells were stimulated with phorbol myristate acetate (50 ng/mL) for 24 to 48 hours, these K562 cells formed dense cell:cell aggregates. This homotypic aggregation required both activation of the CD11b/CD18 complex and the induction of the counter-receptor for CD11b/CD18 on the conjugate cell. This cell line will (1) enable the structure-function relationships between cell activation and homotypic adherence to be assessed, (2) provide the opportunity to identify accessory molecules required for activation of the CD11b/CD18 complex, and (3) facilitate the identification of novel ligands for the CD11b/CD18 complex.
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PMID:Transfected leukocyte integrin CD11b/CD18 (Mac-1) mediates phorbol ester-activated, homotypic cell:cell adherence in the K562 cell line. 840 Mar

Neutrophil activation is thought to play a major role in the inflammatory response seen in reperfusion injury and similar clinical situations, i.e. extracorporeal circulation. Impairment of neutrophil function or reduction of total numbers of neutrophils using a leucocyte filter may be beneficial in reducing the adverse clinical effects. In this study we have investigated the effect of the Pall LG6 and control AV6 filters during simulated in vitro cardiopulmonary bypass (CPB). Various parameters were evaluated including neutrophils, total leucocytes, monocytes, lymphocytes and platelets, expression of antigens on neutrophils using a panel of leucocyte-associated monoclonal antibodies CD13, 14, 15, 45Ro, 67, 11a, 11b and L selectin. The effects of leucocyte stimulation with phorbol myristate acetate (PMA) and a leucocyte bolus from a patient with chronic myeloid leukaemia (CML) were also investigated. We have demonstrated that the LG6 significantly reduces leucocytes, in particular neutrophils, with a modest reduction of lymphocytes, platelets and haematocrit, whereas the AV6 had no effect on leukocytes or neutrophils in the test system. In addition the LG6 was associated with a reduction in expression of all leucocyte antigens by approximately 20%; however there was no appreciable alteration of any of the antigens with AV6. Leucocyte stimulation with PMA resulted in a dramatic decrease of all cellular elements and an extra leucocyte load (using CML leucocytes) was not effectively filtered by the LG6 filter. These studies identify the capacity of the LG6 as compared with the AV6 to deplete activated neutrophils in an in vitro simulated cardiopulmonary bypass circuit.
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PMID:Studies of the effect of Pall leucocyte filters LG6 and AV6 in an in vitro simulated extracorporeal circulatory system. 860 Oct 40

PCR amplification of highly polymorphic variable number of tandem repeat (VNTR) sequences could be particularly useful in documentation of engraftment and characterization of chimerism following allogeneic bone marrow transplantation (BMT). We have monitored a 31-year old male patient treated with allogeneic BMT for chronic myeloid leukaemia. The recipient's DNA samples were obtained before the transplant and on day 28, 100 and 150 after BMT. The donor's DNA (patient's sister) was also obtained as a reference. ACT B2 locus on chromosome 6 was chosen for the analysis. In addition a deletion polymorphism locus within the pseudoautosomal region of chromosome X and Y (amelogenin gene) was also analysed. On day 28 after BMT both donor and recipient specific alleles were detected in the recipient's sample. However, on day 100 and 150 the recipient specific alleles were no longer detectable. The aforementioned pattern was observed for both markers analysed. The disappearance of recipient specific alleles correlated with clinical symptoms of chronic graft-versus host disease.
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PMID:[Evaluation of bone marrow grafts and hemopoietic chimerism using PCR hypervariable sequencing with variable number tandem repeat sequences]. 865 40

We have established a human stromal cell line derived from the bone marrow of a patient with chronic myelogenous leukemia in blast crisis. This cell line, designated FS-1, exhibits a fibroblastoid morphology and does not express any hematopoietic cell marker tested. FS-1 is negative for alpha-naphthyl acetate esterase, acetylated LDL, von Willebrand factor, and shows no phagocytosis. This cell line is positive for acid phosphatase, alkaline phosphatase, collagen types I, III, IV, and fibronectin. cDNA from FS-1 cells was subjected to amplification by the polymerase chain reaction to assess the constitutive expression of several cytokine genes. Transcripts for interleukin (IL)-6, IL-7, macrophage colony-stimulating factor (M-CSF), and stem cell factor (SCF) were detected in FS-1 cells. IL-6 and SCF also were detected in the culture supernatants of FS-1 at a concentration of 95 pg/ml and 21.2 pg/ml, respectively. These data show that FS-1, established from a human bone marrow, is a stromal cell line which was not generated using transfection with SV40 T antigen. FS-1 cells may be useful in supporting human hematopoietic cells for experimental manipulation.
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PMID:Establishment and characterization of a novel human bone marrow stromal cell line, FS-1. 872 43

We have studied the role of Ras GTPase activating protein (GAP) in the chronic myeloid leukaemia cell line K562 by downregulating its expression using antisense RNA. This had no effect on cell proliferation and survival, suggesting that other effector molecules mediate these roles of Ras. Differentiation to macrophages following treatment with the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate was found to correlate with a significant increase in expression of GAP in K562 cells. When GAP expression was downregulated by antisense RNA, the degree of macrophage differentiation was increased, implicating GAP in the regulation of macrophage differentiation.
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PMID:Downregulation of Ras gap expression in K562 cells correlates with increased differentiation to macrophages but does not affect cell proliferation or survival. 895 28

Our group recently cloned the cDNA-encoding bomapin, a member of the serine protease inhibitor (serpin) superfamily, from a human bone marrow cDNA library (J Biol Chem 270:2675, 1995). To understand its expression within the hematopoietic compartment, RNA extracted from bone marrow or peripheral blood from normal donors and patients with leukemia was reverse transcribed and analyzed by polymerase chain reaction (PCR). Bomapin PCR products were readily detected in normal bone marrow, which was designated as a medium mRNA level. In peripheral blood, bomapin expression was low or undetectable in normal donors (n = 6) and patients with chronic lymphocytic leukemia (n = 6). Blood from patients with chronic myeloid leukemia (n = 6), chronic myelomonocytic leukemia (n = 6), acute myeloid leukemia (n = 5), and acute lymphocytic leukemia (n = 5) exhibited low to medium levels of bomapin expression. Furthermore, a high level of bomapin expression was detected in one individual with acute monocytic leukemia. These data suggest that bomapin expression may be elevated in hematopoietic cells of monocytic lineage. Therefore, we analyzed the expression of bomapin within cell lines that exhibited characteristics of the monocytic lineage. Bomapin PCR products were detected in the monocytic THP-1 and AML-193 cell lines but not in CRL 7607, CRL 7541, KG-1, or K562 cells. Induction of bomapin transcripts was not detected in the latter series of cell lines following a 24-hour treatment with phorbol myristate acetate (PMA, 10(-8) mol/L) or tumor necrosis factor-alpha (TNF-alpha, 30 U/mL), whereas treatment of THP-1 or AML-193 cells with these agents reduced the intensity of the bomapin PCR products. Northern blotting confirmed these results and showed that the expression of bomapin in THP-1 cells was downregulated over a 4-day period by PMA and, to a lesser extent, TNF-alpha. Immunoblotting was used to show the presence of a 40-kD protein in THP-1 cytosol preparations. Bomapin antigen levels were correspondingly reduced after treatment with PMA. Because PMA and TNF-alpha induce monocytic differentiation in THP-1 and AML-193 cells, these data increase the possibility that bomapin may play a role in the regulation of protease activities specifically in early stages of cellular differentiation.
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PMID:Expression of bomapin, a novel human serpin, in normal/malignant hematopoiesis and in the monocytic cell lines THP-1 and AML-193. 945 55

It is suggested that monocytes in patients with chronic myelomonocytic leukaemia (CMML) or chronic myeloid leukaemia (CML) with monocytosis have morphological/functional abnormalities which cause inaccurate counting in automated analysers. In this study, monocytes in 21 normal and 14 CMML blood samples were subjected to morphological analysis and were counted by the manual reference method, three automated analysers and esterase staining. Morphological analysis showed no significant difference between control and CMML monocytes. The alpha-naphthyl acetate esterase scores, a measure of monocyte function, showed a reduction of 40% in CMML monocytes compared to controls. Counts by analysers showed that the Sysmex NE 8000 was the least accurate for CMML monocyte counts and that the Coulter STK-S and Sysmex SE 9000 gave results closer to the manually counted standards.
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PMID:Monocyte analysis in chronic myelomonocytic leukaemia. 962 33

Neutrophils from patients with Chronic Myeloid Leukemia (CML) exhibit defects in several functions. They also show altered phosphorylation-dephosphorylation patterns of several proteins on stimulation with phorbol myristate acetate--a direct activator of protein kinase C (PKC). Since PKC mediates several functions of the neutrophil, in this study we investigate the PKC isoform profile and subcellular distribution in normal and CML neutrophils in an attempt to elucidate their role in CML signalling. Our results show the presence of PKC alpha, betaI, betaII and delta in both the cell types. A distinct and clear signal was obtained for PKC alpha, the isoform reported to be absent or present in very low amounts in normal neutrophils. In addition, PKC alpha was present in significantly lower levels in CML neutrophils while the PKC delta isoform was found in significantly higher amounts in the CML cytosol as compared to that in normal cells. PKC alpha, betaI, betaII and delta isoforms could not be detected in the nucleus of unstimulated normal and CML neutrophils. The altered levels of PKC alpha and delta may be one of the causes for the defects in function exhibited by the leukemic cells.
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PMID:Protein kinase C isoforms in normal and chronic myeloid leukemic neutrophils. Distinct signal for PKC alpha by immunodetection on PVDF membrane, decreased expression of PKC alpha and increased expression of PKC delta in leukemic neutrophils. 968 Jan 9

We investigated tyrosine phosphorylation of proteins in primary human leukemia cells stimulated by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3), tumor necrosis factor (TNF), thrombopoietin (TPO) and phorbol myristate acetate (PMA) in 61 patients with acute myeloid leukemia (AML), nine patients with chronic myeloid leukemia (CML) in blastic crisis and four patients in chronic phase, and compared these data of leukemia with those of normal human immature hematopoietic cells. These cytokines and PMA induced tyrosine phosphorylation of proteins in a manner characteristic for each cytokine or PMA in AML cells. G-CSF, GM-CSF and IL-3 frequently phosphorylated p92, p80, p70, p44 and p42. p95 was frequently phosphorylated by G-CSF, and was phosphorylated in one third of the cases by TPO. On the other hand, TNF selectively induced tyrosine phosphorylation of p42, and PMA selectively induced that of p44 and p42. In marked contrast to AML cells, CML cells responded poorly to cytokines with protein tyrosine phosphorylation, and normal human bone marrow mononuclear cells and CD34-positive cells also showed poor response to cytokines. The results of the immunoprecipitation studies showed tyrosine phosphorylation of signal transducers and activators of transcription (Stat) 5 induced by G-CSF, GM-CSF, IL-3 and/or TPO in six cases, that of extracellular signal-regulated kinase (ERK) by GM-CSF in two cases and that of p38 by TNF in three cases. Intracellular amount of Stat5 was markedly increased in AML cells compared with that in CML cells and normal human bone marrow cells. whereas intracellular amount of ERK and p38 was uniformly abundant in both leukemic and normal cells. These results show cytokine-specific and amplified tyrosine phosphorylation of proteins in AML cells and suggest that amplified response might, at least in part, result from the increased amount of signaling molecules such as Stat5.
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PMID:Tyrosine phosphorylation of proteins in primary human myeloid leukemia cells stimulated by cytokines: analysis of the frequency of phosphorylation, and partial identification and semi-quantification of signaling molecules. 988 38

The occurrence of acute transformation during the treatment of chronic myeloid leukemia (CML) is still a poorly understood mechanism. In this disease p53, p16INK4A, p15INK4B, p57KIP2 mutations and p15INK4B/p16INK4A homo/hemizygous deletions were analyzed in the initial diagnosis phase and during the treatment phase of twelve CML cases, in order to establish whether there was a consistent molecular genetic alteration in its progression. During the treatment period, four of twelve cases had blastic crisis. All the mutations observed in p53, p16INK4A and p15INK4B cumulated in three out of four CML cases who had blastic crises. In one case, p53 codon 282 mutation (CGG-->TGG; arg-->trp) were observed in initial diagnosis. Seven months later, G-->C transition in the 3' side of p15 cDNA (778. nucleotide) was observed in the accelerated phase with the same p53 codon 282 mutation. Thirteen months later, this patient died as a result of blastic crisis. The patient in blastic crises in the initial diagnosis phase had a mis-sense point mutation in p16 codon 69 (ACT-->AGT; thr-->ser) and a polymorphism in codon 68 (GCC-->GCG). Six months later, this patient also died. In one case, p53 codon 237 mutation (ATG-->ATA; met-->ile) were observed in the initial diagnosis phase. Then months later, the patient died as a result of blastic crises. No p15INK4B/p16INK4A homo/hemizygous deletion and p57KIP2 gene mutation which was described in the same pathway were observed in CML progression. These results indicate that p15INK4B and p16INK4A gene alterations may have an affect on the progression of CML-like p53 mutation. A correlation was found with the progression of CML and p53, p15INK4B and p16INK4A somatic mutations. Finding p15INK4B and p16INK4A gene alteration as well as p53 mutations may be a prognostic marker in patients with CML.
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PMID:P53, p15INK4B, p16INK4A and p57KIP2 mutations during the progression of chronic myeloid leukemia. 1006 44


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