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)

FcRIII (CD16) expression on neutrophils from 17 patients with chronic myeloid leukemia (CML) was studied by flow cytometry using monoclonal antibodies. A variable proportion of CD16-negative neutrophils were found both in CML patients in chronic phase (3 out of 8 patients) and in CML patients in hematological remission (3 out of 9 patients). Neutrophils with reduced FcRIII expression showed more defective chemiluminescence and phagocytosis than neutrophils with normal FcRIII expression. Circulating myeloid cells from three patients in chronic phase, showing a normal percentage of CD16-positive neutrophils, were isolated and fractionated by discontinuous Percoll gradients. This study showed that CD16 appears at the stage of metamyelocyte, that band cells and segmented neutrophils display an identical pattern of membrane FcRIII, and that the fluorescence intensity shown by metamyelocytes is different from that displayed by more mature cells. The association between low FcRIII expression and function abnormality could be suggestive of a defect in CML neutrophil maturation.
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PMID:FcRIII (CD16) expression on neutrophils from chronic myeloid leukemia. A flow cytometric study. 146 30

We have analyzed the ability of highly purified preparations of human NK cells to produce CSF. NK cells, purified by negative selection from 10-d cultures of PBMC incubated with irradiated B-lymphoblastoid cell lines, were stimulated with rIL-2, FcR(CD16) ligands (particulate immune complexes or anti-CD16 antibodies bound to Sepharose), a combination of CD16 ligands and rIL-2, or the phorbol diester phorbol dibutyrate (PDBu) together with the Ca2+ ionophore A23187. Both rIL-2 and CD16 ligands induce accumulation of GM-CSF mRNA in NK cells and the combined effect of the two stimuli is synergistic. Maximal accumulation of GM-CSF mRNA is observed after PDBu/A23187 stimulation. The participation of contaminant T cells in the observed expression of the GM-CSF gene is excluded because CD16 ligands do not stimulate T cells and CD3 ligands, powerful stimulators of T cells, are inactive on NK cells. Accumulation of CSF-1 mRNA is observed only in NK cells stimulated with both CD16 ligands and rIL-2, whereas accumulation of IL-3 mRNA is observed only in NK cells stimulated with PDBu/A23187. Transcripts of the G-CSF, IL-1 alpha, and IL-1 beta genes were never detected in NK cells in these experiments. The kinetics of accumulation of GM-CSF and CSF-1 mRNA in NK cells stimulated with CD16 ligands and rIL-2 peaked at 2-4 h and was slower than that of TNF and IFN-gamma mRNA, which peak at 1 h. GM-CSF was precipitated from the supernatant fluids of NK cells stimulated with PDBu/A23187 and its biological activity was demonstrated by the ability of the supernatants to sustain proliferation of the TALL-101 cell line or CML blasts. Biological activity of IL-3 and CSF-1 was demonstrable in supernatant fluids of NK cells stimulated with PDBu/A23187 and CD16 ligands/rIL-2, respectively.
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PMID:Production of hematopoietic colony-stimulating factors by human natural killer cells. 252 57

We describe for the first time a case report documenting a chronic myelogenous leukemia (CML) patient who developed a blast crisis of natural killer (NK) lymphocytes. Many of the blasts exhibited large granular lymphocytic (LGL) morphology. Single parameter immunophenotyping results determined that the granulated as well as the agranulated blast cells were NK lymphocytes (CD45, NKH1, CD2, LEU 17, and CD16 positive; CD3, CD8, and LEU 7 negative). Dual parameter flow cytometric testing also determined that some of the blasts expressed the CD11b and CD11c markers as reported for some types of NK lymphocytes. Approximately 10% of the cells were in the S phase of the cell cycle as determined by a modified Vindelov DNA content analysis test and may theoretically reflect some of those cells expressing CD11b and CD11c. The cells did not express in vitro NK lymphocyte functional activity against a K562 target and therefore similar to other reported cases of presumably immature NK lymphocytic leukemias. The NK lymphocyte blast crisis was successfully treated with vincristine and prednisone. The patient's disease eventually relapsed and transformed to a progenitor stem cell before she died (CD45, 13, CD38, and CD34 positive). The flow cytometric immunophenotyping results contributed significantly as an important adjunct in determining the appropriate diagnosis, helping to select the type of therapy, and monitoring the patient with this unusual type of blast crisis.
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PMID:Natural killer lymphocyte blast crisis of chronic myelogenous leukemia. 281 23

Natural killer (NK) cells in CGL were measured phenotypically (by Leu7 and CD16 Mab staining) and functionally (by a standard chromium-release cytotoxicity assay) in eight patients before and during alpha-IFN therapy. Before alpha IFN therapy, phenotypic NK cells were normal in relative and absolute numbers but were consistently defective functionally; this defect was partially corrected by in vitro exposure to alpha IFN. During alpha IFN therapy, there was no change in NK function in five patients and enhanced (two patients) or reduced (one patient) activity was observed in the other three. Cold-target inhibition experiments showed no evidence of NK binding to normal or CGL myeloid progenitors. It is concluded that alpha IFN-enhanced NK function, a known anti-tumour mechanism in animal models, is probably not the basis of the responsiveness of CGL to alpha IFN therapy.
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PMID:The beneficial effects of alpha IFN in CGL are probably not mediated by NK cells. 292 9

We have demonstrated that unstimulated highly-enriched NK cells have the capability to inhibit the growth of fresh clonogenic leukemic cells from AML, CML and preleukemic patients. The NK-cell population mediating antileukemic reactivity exhibited LGL morphology and NKH1 and CD16 phenotype. The inhibition of leukemic growth could be mediated by cell-to-cell contact or by soluble factor produced by NK cells. Antileukemia activity was only detectable when enriched population of LGL was utilized; NW-filtered lymphocyte population did not exhibit leukemia-inhibitory effect. However, such activity could be generated after culture of the latter effector cells with IL-2. The leukemia directed IL-2 activated effector cells were characterized as NK cells. The data reported here provide new insight into host factors which may control leukemia growth and indicate the possible future application of NK cells for therapy of leukemia.
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PMID:Inhibition of clonogenic growth of fresh leukemia cells by unstimulated and IL-2 stimulated NK cells of normal donors. 350 Oct 42

Changes in the intracellular Ca2+ levels of human large granular lymphocytes (LGL), loaded with the fluorescent Ca2+ indicator fura-2, have been studied upon addition of human chronic myelogenous leukemia K562 cells. The measurements, analyzed at the single-cell level using image analysis, indicate a rapid Ca2+ mobilization in the effector cell upon interaction with its target cell. This mobilization appeared to be localized to an area within the effector cell that was in physical contact with target cells. The LGL responded with different kinetics in a transient manner and about 19% of them could undergo two or more responses. Data obtained from experiments performed with anti-CD16- and anti-CD18-pretreated LGL in the presence of target cells indicate that the CD16 and CD18 molecules are not likely to be the triggers of the Ca2+ response, although they might participate in the recognition of the target cell.
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PMID:Rapid Ca2+ mobilization in single LGL cells upon interaction with K562 target cells--role of the CD18 and CD16 molecules. 767 26

Donor-derived cell-mediated immunotherapy has been shown to be an effective tool for reinduction of remission in chronic myeloid leukaemia (CML) patients who have relapsed post-bone marrow transplantation (BMT). Linomide, quinoline-3-carboxamine (LS 2616), is a new immunomodulator shown to increase the number of NK precursors in mice in addition to upregulating the quantity of CD56(+), CD3(-) and CD16(+) NK cells in the peripheral blood of patients following autologous BMT (ABMT). We investigated the in vitro effects of Linomide on NK activity of normal human donors. Large granular lymphocytes (LGLs) and NK cells were incubated overnight with Linomide (0.02-4.8 mg/ml), recombinant human interleukin-2 (IL-2, 75 IU/ml), or a combination of both. Linomide, at 0.02-0.3 mg/ml, augmented IL-2-induced proliferation of LGLs and NK cells in an inversely proportional manner. In contrast, Linomide at 0.6-4.8 mg/ml inhibited IL-2-induced proliferation of LGLs and NK cells in a dose-dependent manner. Linomide was able to potentiate phytohemaglutinin-induced CD3(+) cell proliferation. In addition, supernatants derived from Linomide treated CD3(+) T cells were able to mimic the direct stimulatory effect of Linomide on activated NK cell proliferation. These supernatants were found to have low levels of tissue necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) and therefore Linomide stimulation of NK and T cell proliferation may be due to its inhibitory effect on the secretion of these cytokines by activated CD3(+) T cells. Linomide had no effect on cytotoxicity nor on the phenotypic expression of resting and IL-2-activated LGLs or NK cells. In view of our results, Linomide could possibly play a potential role in adoptive cell-mediated immunotherapy post-BMT.
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PMID:The novel immunomodulator, Linomide, stimulates interleukin-2-induced human natural killer (NK) cell and PHA-stimulated T cell proliferation from normal donors. 863 78

Natural killer (NK) cells are a distinct non-T, non-B lineage of lymphocytes that mediate major histocompatibility complex-unrestricted cytotoxicity. Morphologically they are large granular lymphocytes, and phenotypically they commonly express CD16 and CD56 antigens, without expressing cell surface CD3. Although the developmental pathway of NK cells is not fully understood, they arise from CD34+ hematopoietic stem cells and, at least in part, differentiate in the bone marrow. They gain byctoplasmic CD3 gamma delta epsilon zeta antigens during maturation, and lose cytoplasmic CD3 gamma delta epsilon thereafter until the terminal maturation. Lymphoproliferative disorders of NK cells include NK cell-lineage granular lymphocyte-proliferative disorders (NK-GLPD), NK-cell lymphoma, and acute leukemia of NK-cell lineage. NK-GLPD are relatively rare. Most patients exhibit a chronic indolent clinical course, and do not require specific treatment. However, some patients exhibit an aggressive clinical course, and die of the disease despite extensive chemotherapy. This aggressive type NK-GLPD is caused by Epstein-Barr virus (EBV). Patients with NK-cell lymphoma are rare, and often exhibit necrotic lesion and angiocentric morphology. This tumor is mainly found in the nasal tract, but the true incidence of NK-cell lymphoma in nasal lymphomas is not known. Probably many lymphomas arising from the nasal cavity, but not from paranasal sinuses, are of NK-cell lineage. NK-cell lymphoma is also caused by EBV, and is resistant to combination chemotherapy. Acute leukemia of NK-cell lineage is very rare. Several cases of acute lymphoblastic leukemia and a single case of blast crisis of chronic myelogenous leukemia have been documented to have leukemic blasts characteristic of NK cells. However, the precise lineage and differentiation stage of the leukemic blasts have not been delineated.
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PMID:Lymphoproliferative disorders of natural killer cells. 876 11

Using flow cytometry, we quantitatively examined the density of the CD16 (IgG Fc receptor III) antigen on neutrophils in healthy control subjects, in patients with neutrophilia due to bacterial infection, and in patients with chronic myeloproliferative disorders (chronic myeloid leukemia [CML], polycythemia vera, or essential thrombocythemia). The density was expressed as the mean fluorescence intensity of neutrophils stained with fluorescein isothiocyanate-labeled anti-CD16 monoclonal antibody. We also determined leukocyte alkaline phosphatase activity semiquantitatively in the same population. The mean (+/- SD) density of the CD16 antigen on neutrophils in patients with CML (n = 13; 240.4 +/- 134.8) was lower (P<.001 ) than in healthy control subjects (n = 25; 656.6 +/- 238.0), and the density was also lower than in patients with bacterial infection (n = 15; 671.5 +/- 288.1), polycythemia vera (n = 7; 552.6 +/- 99.9), or essential thrombocythemia (n = 11; 671.5 +/- 411.5). The density of the CD16 antigen was 300 or more in all healthy control subjects and in all patients examined, except for those with CML. The CD16 antigen density was less than 300 in 10 of the 13 patients with CML. Leukocyte alkaline phosphatase activity was also low in 10 of the 13 patients with CML. These findings indicate that flow cytometric analysis of the density of neutrophil CD16 antigen is useful for the differential diagnosis of CML from other chronic myeloproliferative disorders.
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PMID:CD16 antigen density on neutrophils in chronic myeloproliferative disorders. 953 1

Expression of alkaline phosphatase (ALP) on the surface membrane of neutrophils (mNAP) was studied by immunofluorescence using an anti-ALP monoclonal antibody. Fluorescent intensity distribution of mNAP was analyzed using FACS (fluorescence-activated cell sorter). The mean fluorescent intensity (MFI) of the mNAP in this assay was well correlated with the neutrophil ALP (NAP) score demonstrated cytochemically (r = 0.832). mNAP levels in various hematological disorders were evaluated by % mNAP+ cells and MFI. The levels in aplastic anemia and polycythemia vera were significantly higher, and in chronic myelocytic leukemia and paroxysmal nocturnal hemoglobinuria (PNH), the levels were significantly lower compared with the levels in healthy volunteers. Two-color immunofluorescence with anti-ALP and anti-CD16 showed that the PNH clone was essentially negative for mNAP, whereas residual normal neutrophils (CD16+) had levels slightly higher than those in normal individuals. Highly reproducible results were obtained in the blood samples which were stored at 4 degrees C for at least 24 hr without any treatment prior to immunofluorescent staining. No degradation of fluorescent intensity was seen 4 days after staining and fixation. The mNAP assay is simple, without subjective evaluation for quantification, and is useful for differential diagnosis of hematological disorders.
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PMID:Assessment of alkaline phosphatase on the surface membrane of neutrophils by immunofluorescence. 988


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