UNIPROT:P10721 - FACTA Search

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Query: UNIPROT:P10721 (c-kit)
6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD34+ cells were enriched, using a panning method, from peripheral blood (PB) and bone marrow (BM) of healthy volunteers and of patients treated with chemotherapy plus granulocyte colony-stimulating factor (G-CSF). In healthy volunteers, PB CD34+ cells expressed CD33 and CD13 at a higher frequency than BM CD34+ cells, and PB CD34+ cells contained a greater number of burst-forming units-erythroid (BFU-E) than colony-forming units granulocyte-macrophage (CFU-GM). Administration of G-CSF to healthy volunteers induced a marked increase in the number of PB CD34+ cells, although the proportions of those expressing CD33, CD13, and c-kit among these cells as well as colony-forming ability were not changed before and after G-CSF administration. There were no significant differences in surface antigens on PB CD34+ cells between healthy volunteers and patients after chemotherapy plus G-CSF, except for low expression of c-kit in the PB of patients. However, PB CD34+ cells from patients contained almost the same number of CFU-GM as BFU-E. These results indicate that there were clear differences in the features of CD34+ cells from BM and from PB, and between healthy volunteers and patients after chemotherapy plus G-CSF. Enriched CD34+ cells are useful for analyzing the characteristics of hematopoietic progenitor cells, and such analysis may predict the usefulness of autologous or allogeneic peripheral blood stem cell transplantation.
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PMID:Characterization of enriched CD34+ cells from healthy volunteers and those from patients treated with chemotherapy plus granulocyte colony-stimulating factor (G-CSF). 754 13

Both normal and leukaemic human megakaryocytopoiesis are stimulated by several cytokines, including stem cell factor, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3, GM-CSF/interleukin-3 fusion protein, interleukin-6, interleukin-11, basic fibroblast growth factor and thrombopoietin, but are inhibited by tumour necrosis factor-alpha, platelet factor 4, beta-thromboglobulin, thrombin, interleukin-4, interferon-alpha and interferon-gamma. Human megakaryoblastic leukaemia cell lines have common biological features, including high expression of the megakaryocytic specific antigen: CD41; high expression of the early myeloid antigens: CD34 and CD33; constitutive expression of interleukin-6 and platelet-derived growth factor; complex karyotype picture; expression of c-kit: the stem cell factor receptor; growth-dependency or -stimulation by stem cell factor, interleukin-3 and/or GM-CSF; megakaryoblastic differentiation by phorbol-myristate-acetate; and in vivo tumorigenicity in mice is associated with marked fibrosis. Only a few agents including phorbol-myristate-acetate; vitamin D3, interferon-alpha, interferon-beta 2, erythropoietin and thrombin have been reported to induce megakaryocytic differentiation in the human megakaryoblastic leukaemia cells.
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PMID:Characteristic biological features of human megakaryoblastic leukaemia cell lines. 756 68

A novel fibroblast-dependent human immature megakaryoblastic leukemia cell line (M-MOK) was established from the bone marrow of a girl with acute megakaryoblastic leukemia, and its growth was determined to be completely dependent on the presence of human embryonic lung-derived fibroblasts, HEL-O. Adhesive interaction between M-MOK and HEL-O was crucial for viability; once HEL-O was removed from the culture, mortality was total within a few days. On HEL-O cells, M-MOK could be passaged for more than 2 years. With regard to surface marker profile, the established cells were positive for CD11a, CD13, CD18, CD33, CD34, CD41b, CD42b, CD54, and c-kit antigens, but negative for HLA class II antigen and glycophorin. Histochemically, the cells were negative for myeloperoxidase, nonspecific esterase, and naphthol ASD chloroacetate esterase staining. Electron-microscope examination revealed the cells to be negative for platelet peroxidase (PPO). After induction of differentiation by a phorbol ester, however, the cells were demonstrated to be positive for PPO with a morphological change to megakaryocytes. From these results, M-MOK was considered to represent an immature cell line of megakaryocyte lineage. Studies of the mechanisms sustaining the HEL-O-dependent continuous in vitro growth of M-MOK cells revealed the following results: (1) M-MOK could grow even when separated from HEL-O by a nucleopore membrane; (2) conditioned medium (CM) from HEL-O supported the growth of M-MOK for more than 1 month without feeder cells; (3) the growth of M-MOK on HEL-O or CM supplement was nearly entirely inhibited by anti-GM-CSF (1 microgram/mL); (4) GM-CSF mRNA was detected in HEL-O cells; and (5) HEL-O was found to secrete GM-CSF into the culture medium. Taken together, the growth of M-MOK might therefore be driven by a soluble factor, that is, GM-CSF secreted from HEL-O cells. The presence of HEL-O, however, inhibited anti-GM-CSF-induced M-MOK death. Co-culture of M-MOK and HEL-O cells thus offers a useful experimental model for analysis of interactions between hematopoietic stem cells and stromal cells.
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PMID:Establishment and characterization of a novel human immature megakaryoblastic leukemia cell line, M-MOK, dependent on fibroblasts for its viability. 758 86

Human cord blood or bone marrow cells expressing the CD34 surface antigen include a population of pluripotent progenitors. We identified and isolated a subpopulation of cells coexpressing CD34 and c-kit, a transmembrane receptor with tyrosine kinase activity. Novel monoclonal antibodies (16A6, 14A3, 3D6) directed against the extracellular domain of c-kit were used for immunofluorescence labeling and sorting of low-density mononuclear cells (MNCs) from umbilical cord blood and bone marrow. The frequency of c-kit-labeled MNCs from cord blood (mean 5.0% +/- 2.1%, n = 16) was similar to that from adult bone marrow (mean 3.7% +/- 1.3%, n = 4). On average, 1.4% of CD34-positive cells were recorded in cord blood and 2.1% in bone marrow MNCs. Roughly 60% of CD34-positive cells coexpressed c-kit. The ability of CD34+/c-kit+ cells to form multilineage colonies (CFU-GEMM) was assayed after sorting with an antibody that did not show any significant effect on c-kit ligand (RL) or granulocyte/macrophage colony-stimulating factor (GM-CSF)-induced colony formation. For CD34+/c-kit+ cells, we found a 20- to 50-fold enrichment as against total MNCs, and a 2-fold enrichment if compared with the CD34+/c-kit-population. To study expression of c-kit in lymphocytic precursors, monoclonal anti-CD7 or anti-CD10 antibodies were used simultaneously. In contrast to CD34-expressing cells, however, no consistent double-labeled subpopulation of lymphocytic cells was detected. Furthermore, coexpression of CD38 (73% +/- 14%, n = 4) or CD33 (29% +/- 12%, n = 5) on a majority of c-kit-positive cells showed their lineage commitment to erythropoiesis and granulocytopoiesis.
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PMID:Characterization of hemopoietic cell populations from human cord blood expressing c-kit. 767 90

To investigate how c-kit and c-kit ligand play a role in the function of hematopoietic stem cells, we determined the expression of c-kit in sorted human hematopoietic stem cells, CD34+CD33- cells and CD34+CD33+ cells. CD34+ cells constituted approximately 1% of the population of gated bone marrow cells and contained colony-forming cells. Two-color analysis by a fluorescence-activated cell sorter (FACS) revealed that about one-third to one-half of the total CD34+ cell population were positive for the CD33 antigen. To analyze the relative accumulation of c-kit mRNA in sorted cells, we used the reverse transcription-polymerase chain reaction (RT-PCR) method, followed by Southern blot analysis. There was a linear relationship between the amount of input RNA and products amplified in the range of 10(3) to 10(5) cells. Using this procedure, we carried out an analysis of c-kit mRNA expression in CD34+CD33-, CD34+CD33+, CD34-CD33+, and CD34-CD33- cells. Enhanced expression for c-kit mRNA was observed solely in CD34+CD33- cells. In contrast, flow cytometry shows that c-kit protein was expressed most abundantly in CD34+CD33+ cells. Colony-forming cells were generated on a human stromal cell layer for 5 weeks initiated with CD34+CD33- cells but not with CD34+CD33+ cells. During co-culture with stromal cells, CD34+CD33- cells differentiated into CD34+CD33+ cells. From these findings, it is concluded that CD34+CD33+ cells are direct progenies of CD34+CD33- cells. In this differentiation pathway, the expression of c-kit mRNA decreased and the c-kit protein increased.
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PMID:Expression of c-kit mRNA and protein during the differentiation of human hematopoietic progenitor cells. 768 19

The diagnostic and prognostic value of immunophenotyping with 18 murine monoclonal antibodies (MoAbs) to a variety of leukocyte differentiation antigens was assessed in 168 adults aged 15 to 60 years with acute myeloid leukemia (AML). Patients were entered on the multicentre Australian Leukaemia Study Group M4 protocol, and were randomized to receive either standard or high-dose Ara-C together with daunorubicin and etoposide as induction chemotherapy, followed by standard consolidation and maintenance therapy. Diagnostic bone marrow aspirate (152 cases) or peripheral blood samples (16) were analyzed by indirect immunofluorescence and flow cytometry. MoAbs used were directed at myeloid (CD11b, CD13, CD14, CD15, CD33, CD41), lymphoid (CD2, CD3, CD7, CD9, CD10, CD19), or stem cell (HLA-DR, CD34, c-kit receptor) antigens, as well as the leukocyte integrins CD18 and CD49e, and the transferrin receptor CD71. Of the myeloid markers, CD13 and CD33 were the most useful diagnostically (71% and 79% of cases positive, respectively), with CD11b, CD14, and CD15 less commonly positive. A minority of cases expressed lymphoid antigens, either T cell (CD2 16%, CD3 7%, CD7 28%) or B cell (CD10 2%, CD19 7%). CD34 was detected on 42% and c-kit receptor on 48%. When patients were analyzed for response to treatment, CD2, CD9, and CD14 were significantly associated with complete remission rate: cases expressing these antigens had a poorer response than negative cases. In univariate analysis, CD11b+ cases had shorter periods of remission (relative risk of relapse, 2.33; P = .003) and shorter survival (relative death rate, 1.91; P = .006). In multivariate analysis, adjusting for other prognostic factors, CD9 and CD11b were significantly predictive of shorter survival. No other marker had a significant predictive effect. We conclude that myeloid MoAbs are useful in confirming the diagnosis of AML, but their prognostic value may be limited to CD11b. Lymphoid antigen expression is a consistent phenomenon in a minority of cases of AML, but appears to have little clinical significance.
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PMID:Prognostic value of immunophenotyping in acute myeloid leukemia. Australian Leukaemia Study Group. 804 37

The phenotypic and biologic properties of malignant cells in a case of aggressive mastocytosis with multi-organ involvement, circulating mast cell precursors and absence of skin infiltrates were analyzed. Circulating mast cell precursors were detected by immunostaining using antibodies against mast cell tryptase as well as by electron microscopy. These progenitors were tryptase+/chymase- (MCT) and accounted for 10 to 20% of nucleated mononuclear blood cells (MNC). A subset of them contained metachromatic granules. As assessed by combined toluidine blue/immunofluorescence staining, the granulated mast cell precursors were found to express CD9 (P24), CD33 (gp67) and CD44 (Pgp-1), but not basophil-related markers (CD11b (C3biR), CDw17 (lactosylceramide), CD123 (il-3R alpha))or monocyte-related antigens (CD14, CD15). Expression of the mast cell growth factor (MGF) receptor, c-kit(CD117), was also demonstrable, whereas the skin mast cell marker C5aR (CD88) could not be detected on mast cell precursors. The ligand of c-kit, recombinant human (rh) stem cell factor (SCF = MGF), induced histamine release from circulating mast cell progenitors, whereas rhC5a, a potent skin mast cell-/basophil-agonist, was ineffective over the dose-range (10(-9) to 10(-7(M)) tested. Analysis of mast cell antigens in malignant mastocytosis or mast cell leukemias may be helpful to establish a diagnosis and to determine the phenotype of the clone.
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PMID:A case of malignant mastocytosis with circulating mast cell precursors: biologic and phenotypic characterization of the malignant clone. 855 22

A novel human leukemia cell line (Kasumi-3) was established from the blast cells of a 57-year-old man suffering from myeloperoxidase-negative acute leukemia. The cell line had five distinctive features, as follows. 1) Flow cytometric analyses showed cell surface expression of CD7, CD4, CD13, CD33, CD34, HLA-DR and c-Kit. This phenotype is compatible with that of acute myelocytic leukemia cells with the M0 subtype in the French-American-British classification. 2) Kasumi-3 cells carried chromosomal abnormalities of t(3;7)(q27:q22), del(5)(q15), del(9)(q32), and add(12)(p11). The breakpoint of 3q27 was located near the EVI1 gene, and a high level of expression of the EVI1 gene was observed. 4) Kasumi-3 cells treated with TPA showed maturation to monocytic lineage. 5) Treatment with either interleukin (IL)-2, IL-3, IL-4, granulocyte-macrophage colony-stimulating or stem cell factor induced the proliferation of Kasumi-3 cells. Thus, the Kasumi-3 cell line shows the characteristic features of undifferentiated leukemia. It should, therefore, be useful both for studying the biological characteristics of acute myelogenous leukemia M0 subtype and for investigating the role of the EVI1 gene in leukemogenesis.
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PMID:Establishment of an undifferentiated leukemia cell line (Kasumi-3) with t(3;7)(q27;q22) and activation of the EVI1 gene. 861 29

We report our observations with the cell line LW/SO, which was recently derived from the bone marrow of a patient with acute myeloid leukemia. Based on the morphological and histochemical examination, the leukemic cells were classified primarily as FAB type M4. However, 2 years later, in relapse, the cells changed their morphology and were hence specified as FAB type M2 (slightly positive for acid phosphatase and Sudan black). The cells established have now been in culture for approximately 11 months and display nearly 100% CD4/5/7/15/25/71/120a,b at varying densities. Some of them spontaneously and reversibly become either CD34 + /38- or CD34 - /38+, yet the majority of the cells remain negative for both. All attempts to separate the cells with a distinct phenotype by limiting dilution or sorting through a flow cytometer failed repeatedly. The subsets, enriched up to 98% (regardless of their primary immunophenotype CD34 - / 38-, CD34 + /38-, or CD34 - /38+), soon displayed a phenotypical constellation similar to that before sorting. The ratio of CD34- to CD34+ seems to be influenced by the cell density: The greater the cell-to-cell contact, the lower the percentage of CD34-expressing cells. Some of the cells apparently differentiate into T-cell phenotype and acquire CD3 and T-cell receptor (TCR) alpha/beta molecules. While the quantity of CD34-expressing cells significantly increased in the presence of dexamethasone (10(-7) M), and some of them additionally acquired CD33 antigen, the percentage of CD3-positive cells was enhanced by adding 1% DMSO in medium. In contrast, cytokines such as IL-1, IL-2, IL-3, IL-4, IL-6, G-CSF, GM-CSF, or SCF (c-kit ligand) altered neither the proliferation capacity nor the phenotypical constellation of LW/SO cells (each tested alone). Although normal karyotype was obtained from the bone marrow cells, the LW/SO cells revealed a homogeneous chromosomal composition of 45, X, -X, der(9) inv(9) (p12q13) del(9) (p22?). These data suggested that LW/SO cells might be the leukemic counterpart of putative pre-CD34-positive progenitors. In order to substantiate this assumption, we analyzed the expression of other so-called T-cell markers on CD34+ cells from peripheral blood stem cell aphereses of five patients who later underwent high-dose chemotherapy and subsequent stem cell retransfusion. These data clearly revealed that a considerable amount of CD34+ hematopoietic progenitors co-express CD2/4/(5)/(7)/25 at an early stage of differentiation, and support the notion that CD34-negative LW/SO cells with the surface markers CD4/5/7/25 are probably phenotypical representatives of pluripotent stem cell. Hence, not all CD34-negative populations with so-called T-cell surface markers should be considered T-cells; some may constitute the ancestor of CD34 antigen-expressing progenitors.
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PMID:LW/SO cell line: a tool for studying the phenotypical characterization and commitment of hematopoietic stem cells. 864 43

To characterize the persistent abnormalities of hematopoiesis in aplastic anemia (AA) after immunosuppression with antilymphocyte globulin (ALG), we analyzed the quantity, phenotype, and growth properties of hematopoietic progenitor cells in 13 patients who received ALG treatment. Flow cytometry (FACS) revealed a deficiency of CD34+ cells in bone marrow (BM) of all patients. This deficiency was most severe (40-fold) in 4 patients in AA relapse. In 9 patients in remission, CD34+ cells were reduced 2-10-fold and showed no correlation with the ALG-induced improvement of peripheral blood cell counts. The proportion of CD34+ cells carrying c-kit receptors was abnormally low (2-10-fold below normal) in 5 of 13 AA patients. These patients also displayed low levels of c-kit mRNA by reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, the CD34+ cell population was almost completely depleted of CD34+CD38- early hematopoietic progenitors in all AA patients. The proportion of CD34+ cells expressing lineage differentiation antigens CD33, CD71, and CD45RA in AA was increased, as compared to control BM. Formation of hematopoietic colonies by FACS-purified CD34+ cells was nearly absent in 4 relapsed patients, normal in 4 of 9, and decreased (up to 10-fold) in 5 of 9 patients in remission. The degree of impairment of colony-forming ability by AA progenitors correlated well with the reduction of CD34+ c-kit+ cells. The best proliferative response of CD34+ cells was observed in the presence of stem cell factor and, in some cases, fit3 ligand. Our results indicate that the disease process in AA depletes immature BM progenitors, thus providing a plausible explanation for persistent defects in colony-forming ability and long-term regenerative capacity of AA marrow after immunosuppression. Analysis of the immunophenotypes and the proliferative properties of purified progenitors may be useful for estimating degree of hematopoietic recovery in ALG-treated patients.
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PMID:Deficiency of CD34+ c-kit+ and CD34+38- hematopoietic precursors in aplastic anemia after immunosuppressive treatment. 870 44

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