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)

Morphologically mature granulocytes from patients with chronic myeloid leukemia show significant impairment in their ability to internalize aggregated IgG, a ligand that is rapidly phagocytosed by normal human granulocytes. With a view to understand the molecular basis of this defect, normal and leukemic granulocytes were examined for the steady-state levels of mRNA for Fc gamma RIII, a membrane-associated receptor that initially binds and traps the IgG-opsonized antigens. Northern blot analyses revealed that the level of the specific mRNA in CML granulocytes was between 0.08 and 0.69 times that seen in the normal granulocytes. This could be one of the contributory factors for the observed endocytic defect in the leukemic granulocytes.
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PMID:Decreased expression of Fc gamma RIII mRNA in leukemic granulocytes. 154 83

Structural and functional characteristics of Fc receptors for IgG (Fc gamma) on human neutrophils were examined with two monoclonal antibody probes specific for the Fc gamma receptors, Leu 11b and 3G8. To determine the distribution, density, and membrane mobility of the Fc gamma receptor, we used immunogold staining techniques, flow cytometry analysis, and fluorescence microscopy. Both 3G8 and Leu 11b inhibited several cell functions, thereby depicting the regulatory role of the Fc gamma receptor in mediating neutrophil activities. Among the functions studied were release of lysosomal enzymes, release of superoxide anion (O2-), and Fc-dependent rosette formation and phagocytosis. The densities of Fc gamma determinants recognized by Leu 11b and 3G8 on cells from a patient with chronic myelogenous leukemia were less than the density of epitopes on neutrophils from a normal individual. Taken together, the detailed analysis of physical and functional aspects of the Fc gamma receptor on neutrophils described in this study serve as a model for further assessment of the use of Fc gamma phenotyping of cells as a diagnostic tool.
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PMID:Fc receptors for IgG on human neutrophils: analysis of structure and function by using monoclonal antibody probes. 241 48

Receptor mediated endocytosis of fluorescein isothiocyanate-conjugated heat-aggregated IgG (Fl-HAIgG) via the receptor for IgG (Fc gamma R) was studied using granulocytes from normal donors and patients suffering from chronic myeloid leukemia (CML). Within 15 min of incubation at 37 degrees C, 75% of the normal granulocytes internalized the ligand, while only 13% of the CML granulocytes could internalize the ligand in the same time. This functional defect was seen in all the CML patients analyzed. To elucidate the reason for this defective endocytosis, the Fc gamma R was isolated from normal and leukemic granulocytes and biochemically characterized, by gel electrophoresis, high pressure liquid chromatography, and one- and two-dimensional peptide mapping. Our results show that the molecule from the two cell types is very similar. The defective endocytosis must therefore be due to events which occur after ligand-receptor binding.
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PMID:The receptor for IgG on human normal and chronic myeloid leukemic granulocytes: functional and biochemical characterization. 252 4

To evaluate the membrane marker profile of human basophils a panel of well-established monoclonal antibodies (MoAbs, n = 60) was used for a combined toluidine/immunofluorescence staining procedure. Myeloid-associated MoAbs (particularly MoAbs against the LFA-1 family (CD11, CDw18), MoAbs directed against lactosylceramide (CDw17), anti-glycoprotein (gp) 150 MoAbs MCS 2 and MY 7 (CDw13), anti-gp 67 MoAb MY 9, anti Fc gamma-receptor (mol wt 40 kd) MoAb CIKM5, anti-CR 1 MoAb E 11, and the antiglycolipid MoAb VIM-2) were reactive with basophils, indicating a close relationship to other mature myeloid cells. Under normal conditions, basophils surprisingly express at least three activation-linked structures not detectable on mature neutrophils, ie, the p45 structure defined by MoAbs OKT-10 and VIP-2b, the p24 structure identified by the CD9 MoAb BA-2, and the receptor for interleukin 2 (IL 2) recognized by three different MoAbs (anti-TAC, IL2RI, anti-IL 2). Moreover, under short-term culture conditions basophils both in mononuclear cell (MNC) suspension and as purified fractions display the HLA-DR and T4 antigens. The neutrophilic/eosinophilic structure 3-fucosyl-N-acetyllactosamine is expressed on basophils only after neuraminidase treatment. Basophils were not stained at all by CD 16 MoAbs directed against the Fc gamma-receptor (mol wt 50 to 70 kd) of neutrophils, by the MoAb 63D3 (CDw12) recognizing the monocyte/granulocyte-associated p 200 antigen, and by the CDw 14 antibodies (VIM-13, Mo 2) defining the monocyte-specific structure p 55. Enriched basophils freshly obtained from chronic granulocytic leukemia (CGL) patients yielded identical results in FACS analyses. In summary, these data indicate that basophils generate a unique combination of surface determinants and possibly represent an activated cell population.
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PMID:Human blood basophils display a unique phenotype including activation linked membrane structures. 311 89

Two new Philadelphia (Ph1) chromosome-positive cell lines, designated KPB-M8 and KPB-M15, were established from the peripheral blood of two patients with chronic myelogenous leukemia in blastic crisis. Both cell lines were characterized by blastic appearance, the presence of acid phosphatase activity, Fc gamma-receptor, and C3-receptor, and reactivity to monoclonal antibodies such as OKM1, MCS2, MY906, MY4 and MY7. These results indicate that KPB-M8 and KPB-M15 cells are of an undifferentiated blast nature. Both cells retained Ph1 chromosome, and showed numerical and structural changes upon chromosomal analysis. These cell lines should provide a useful source for studying differentiation of hemopoietic cells.
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PMID:Establishment of two Ph1 chromosome-positive cell lines, KPB-M8 and KPB-M15. 346 Nov 89

Two different Fc receptors for IgG (Fc gamma R) have been identified on human leukocytes: a high avidity receptor (Fc gamma Rhi) present on monocytes but not on neutrophils, and a low avidity receptor (Fc gamma Rlo) present on neutrophils but not on monocytes. Fc gamma Rlo can be inhibited and the receptor precipitated by monoclonal antibody 3G8. We have used this monoclonal antibody to study the course of Fc gamma Rlo appearance on bone marrow cells, leukocytes of patients with chronic myelogenous leukemia (CML), and HL-60 and U937 cells induced to differentiate with agents such as dimethyl sulfoxide (DMSO), retinoic acid, phorbol myristate acetate, and lymphokine. We report that Fc gamma Rlo is a late differentiation antigen, first expressed at the metamyelocyte stage. Since precursors to metamyelocytes bear Fc gamma R, and the promyelocyte line HL-60 bears Fc gamma Rhi, there must be a progressive loss of Fc gamma Rhi during myeloid differentiation and the reciprocal expression of Fc gamma Rlo. Results of immunoprecipitation and polyacrylamide gel analysis of the proteins are consistent with these results. We have also studied the receptor for the C3bi complement component (CR3), which is blocked and immunoprecipitated by monoclonal antibody OKM10. During DMSO-driven differentiation of HL-60 cells, we find that CR3 is induced on all cells, whereas Fc gamma Rlo is induced on only 24% of cells, suggesting that CR3 appears earlier during differentiation than Fc gamma Rlo does.
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PMID:Ontogeny of Fc receptors and complement receptor (CR3) during human myeloid differentiation. 623 Mar 73

The molecular weights of EDTA-mercaptoethanol-soluble Fc gamma-affined proteins isolated from chronic lymphocytic leukemia of the B type, prolymphocytic leukemia of the B type, chronic myeloid leukemia and hairy-cell leukemia were compared. SDS polyacrylamide gel electrophoresis of the Fc gamma-binding material obtained from all six cases of B type leukemia revealed a single peak with an apparent molecular weight of 28,000. The Fc gamma-affined material isolated from the cells of two cases of chronic myeloid leukemia showed two peaks, one with an apparent molecular weight of 42,600 and one with an apparent molecular weight of 18,800. The Fc gamma-affined material isolated from the cells of two cases of hairy-cell leukemia electrophoresed in the form of a closely spaced double peak. One component of the double peak had an apparent molecular weight of 28,000 and thus corresponds to the Fc gamma-binding material of leukemic B cells. The second component had a slightly lower molecular weight. The latter component is not present on either leukemic B cells or myeloid cells. The results indicate that the EDTA-mercaptoethanol-soluble Fc gamma-affined proteins of different types of cells differ in molecular weight, and thus in molecular structure.
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PMID:Molecular weight analysis of Fc gamma-binding proteins of lymphoid leukemia, myeloid leukemia, and hairy-cell leukemia. 697 74

Morphologically mature granulocytes from patients with chronic myeloid leukemia exhibit a defect in internalization of heat-aggregated IgG. In this study, we investigate the status of the steady-state levels of the mRNA for the two receptors for IgG, Fc gamma RII and Fc gamma RIII, as a step towards understanding the molecular basis of the defect and in turn the discordant maturation of the leukemic cells. Our data show that the mRNA for both receptors is lower in the leukemic cells relative to the normal cells. This may be one of the causes for the defective endocytosis.
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PMID:Decreased expression of both Fc gamma RII and Fc gamma RIII mRNA in leukemic granulocytes. 863 71

Morphologically mature granulocytes from patients with chronic myeloid leukaemia (CML) exhibit a defect in internalization of heat-aggregated IgG. In order to investigate this defect at the molecular level and, in turn, the discordant maturation of these granulocytes, we compared the expression of Fc gamma RII and Fc gamma RIII, the two receptors for IgG on the surface of granulocytes, in normal and CML samples. Our flow cytometric data show that the number of granulocytes expressing Fc gamma RIII is lowered in CML patients to near half that in normal individuals, with a simultaneous decrease in the steady-state levels of the mRNA for Fc gamma RIII. Mean fluorescence intensity (MFI), an indicator of the number of receptors per cell, varies widely for Fc gamma RIII in normal individuals whereas it is more localized and lowered in granulocytes from CML patients. The number of granulocytes positive for Fc gamma RII is also significantly lowered in CML samples compared to the normals, which exhibit a wide variation in the number of cells positive for the receptor, even though their nRNA levels do not vary much. The CML granulocytes, in general, exhibit lowered levels of the steady-state mRNA for Fc gamma RII. The MFI for the surface expression of Fc gamma RII is only marginally different between the two cell types. Our data indicate that the morphologically homogeneous population of CML granulocytes actually consists of at least two types of cells, one which expresses the Fc receptors and one which does not.
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PMID:Fc gamma RII and Fc gamma RIII on normal leukaemic granulocytes: a flow cytometry and northern analysis. 863 83

Advanced glycosylation end-products (AGEs) are believed to play a significant role in the development of vascular complications in diabetic patients. One such product, AGE-LDL, has been shown to be immunogenic. In this report, we describe the isolation and characterization of human AGE-LDL antibodies from the sera of seven patients with Type 1 diabetes by affinity chromatography using an immobilized AGE-LDL preparation that contained primarily the AGE N epsilon (carboxymethyl)lysine (CML, 14.6 mmol/mol lysine), and smaller amounts of N epsilon (carboxyethyl)lysine (CEL, 2.7 mmol/mol lysine). The isolated antibodies were predominantly IgG of subclasses 1 and 3, and considered proinflammatory because of their ability to promote Fc gamma R-mediated phagocytosis and to activate complement. We determined dissociation constants (Kd) for the purified antibodies. The average Kd values (4.76 +/- 2.52 x 10(-9) mol/l) indicated that AGE-LDL antibodies are of higher avidity than oxidized LDL antibodies measured previously (Kd = 1.53 +/- 07 x 10(-8) ml/l), but of lower avidity than rabbit polyclonal LDL antibodies (Kd = 9.34 x 10(-11)). Analysis of the apolipoprotein B-rich lipoproteins isolated with polyethylene glycol-precipitated antigen-antibody complexes from the same patients showed the presence of both CML and CEL, thus confirming that these two modifications are recognized by human autoantibodies. A comparative study of the reactivity of purified AGE-LDL antibodies with CML-LDL and CML-serum albumin showed no cross-reactivity.
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PMID:Autoimmune response to advanced glycosylation end-products of human LDL. 1256 76


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