Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of lineage molecules (CD13 and CD33), c-Kit receptor (CD117), CD34, HLA-DR and adhesion molecule CD49d was assessed in acute myeloid leukemia (AML) blast cells from 32 cases, using direct and indirect quantitative cytometric analysis. High correlation (r=0.8) was found between antigen expression intensity values calculated by direct analysis method (ABC) and by indirect analysis method (RFI). Moreover, the differences in expression intensity of CD13, CD117 and CD34 antigens were found between leukemic and normal myeloblasts. This may be helpful in identification of leukemic cells in the diagnostics of minimal residual disease after treatment in AML patients.
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PMID:Two methods for the quantitative analysis of surface antigen expression in acute myeloid leukemia (AML). 1549 82

TGF-beta, as an inhibitor of hemopoiesis, excreted by hematopoietic stem and progenitor cells, down-regulates the expression of cytokines such as Flt-3 ligand, SCF, IL-3 etc on the stem and progenitor cells. The effect of anti-TGF-beta antibody on ex vivo expansion and expression of adhesive molecules on cord blood CD34(+) cells was studied in this research. The CD34(+) cells from six units of fresh umbilical cord blood were enriched by density gradient sedimentation and purified by miniMACS cell isolation system, and plated them into the SFEM serum free culture system which containing SCF, Flt-3L, TPO and IL-3 in the condition of 37 degrees C, 5% CO2, and saturated moisture. There were three groups in this experiment: (1) blank group: same as the culture system described above; (2) control group: added with normal rabbit IgG into the mentioned culture system; (3) test group: the same culture system with anti-TGF-beta1 antibo-dy. Cultured for 6 days, the number of mononuclear cells (MNC) was counted, the expression of CD34 antigen, CD117 (c-kit) antigen, CD11a antigen, CD49d antigen and CD33 antigen was tested with FCM. Meanwhile, cells of the three groups were plated in the methylcellulose culture system for 14 days, the number of CFU-GEMM, BFU-E, CFU-GM was counted. The results indicated that the expansion multiples of MNC, CD34(+) cells, CD34(+)c-kit(+) cells, CFU-GEMM in the test group (41.82 +/- 13.49, 15.62 +/- 6.95, 13.36 +/- 6.12, 11.07 +/- 4.05) were significantly higher than in the control group (28.86 +/- 9.03, 10.40 +/- 4.98, 9.04 +/- 4.40, 6.36 +/- 2.37) (P = 0.001, 0.002, 0.003, 0.002) respectively. The expansion multiple of more primitive CD34(+)c-kit(-) subpopulation in the test group (69.10 +/- 41.06) was even higher than in the control group (27.29 +/- 10.40) (P = 0.024). Adhesion molecule expression on the CD34(+) cells after short-term expansion: the expression of CD11a on the CD34(+) cells of the original cord blood was (61.73 +/- 4.13)%, and CD49d was (55.12 +/- 5.22)%. After expansion in each group the expression of CD11a on the CD34(+) cells did not change with statistical significance (P > 0.05), the expression of CD49d increased (P < 0.05). Compared with blank group and control group, anti-TGF-beta antibody did not impact on the expression of CD11a and CD49d (P > 0.05). It is concluded that anti-TGF-beta antibody can synergize other cytokines to effectively enhance the proliferation of cord blood NC, CD34(+) cells, progenitor subpopulation of CD34(+)c-kit(-) cells, and increase the output of more primitive progenitor colony, CFU-GEMM and BFU-E. At the same time, anti-TGF-beta antibody did not depresss the expression of adhesion molecules on CD34(+) cells.
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PMID:[Effect of anti-TGF-beta antibody on ex vivo expansion and expression of adhesion molecules of human cord blood CD34+ cells]. 1612 56

We examined the expression of c-kit receptor tyrosine kinase in 195 Thai adult patients with acute leukemia and determined its specificity and predictive values for the diagnosis of adult acute myeloid leukemia (AML). CD117 was used to detect c-kit expression on CD45 and side-scatter-gated blast cells by flow cytometry. Of 163 AML cases, 67% expressed CD117. None of acute lymphoid leukemia (ALL) had CD117 expression, except one case of T-ALL. The majority of AML patients carrying t(8;21), inv(16), and t(15;17) had high CD117 expression. High proportion of AML cases without c-kit expressed monocytic markers. Significant associations between CD117 and CD34 (P<0.001), CD13 (P=0.006), CD7 (P=0.034), and CD19 (P<0.001) were found in AML cases. The calculated specificity of CD117 for the diagnosis of AML was 0.97, which was higher than CD13 (0.78) and CD33 (0.75) but comparable to MPO (0.97). The positive predictive value (PPV) of CD117 for AML was 0.99, with the negative predictive value of 0.35. In conclusion, the majority of Thai adult AML cases expressed c-kit. C-kit is infrequently expressed in ALL and appeared to be specific for AML with high PPV. Future targeting therapy using c-kit as a therapeutic target should benefit the majority of Thai AML patients who had high c-kit expression.
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PMID:C-kit receptor tyrosine kinase (CD117) expression and its positive predictive value for the diagnosis of Thai adult acute myeloid leukemia. 1632 53

Recent data suggest that myeloid neoplasms are organized hierarchically in terms of self-renewal and maturation of early progenitor cells, similar to normal myelopoiesis. In acute myeloid leukemia (AML), the NOD/SCID mouse-repopulating leukemic stem cells usually co-express CD123 with CD34, but lack CD38. So far, however, little is known about expression of other markers and targets on these progenitors. In the present study, expression of target antigens on CD34+/CD38- cells was analysed by multi-color flow cytometry in patients with AML (n = 18), myelodysplastic syndromes (MDS, n = 6), chronic myeloid leukemia (CML, n = 8) and systemic mastocytosis (SM, n = 9). The IL-3Ralpha chain (CD123) was found to be expressed on CD34+/CD38- cells in a majority of the patients in all disease categories. Independent of the type of disease, the vast majority of these stem cells co-expressed aminopeptidase-N (CD13) and CD44 in all patients. By contrast, the CD34+/CD38- progenitor cells expressed variable amounts of the target receptor CD33, c-kit (CD117) and AC133 (CD133). In conclusion, neoplastic stem cells in various myeloid neoplasms appear to express a similar phenotype including target antigens such as CD13, CD33 and CD44. Since many of these targets are not expressed on all stem cells in all patients, the elimination of the entire clone may require combinations of targeted antibodies or use of additional drugs.
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PMID:Detection of molecular targets on the surface of CD34+/CD38-- stem cells in various myeloid malignancies. 1632 50

There is a great need in cell biology for the simultaneous detection of many intracellular and extracellular proteins within single cells. Current optical methods based on fluorescence activated flow cytometry are difficult to multiplex. We have developed a novel application of ICP-MS-linked metal-tagged immunophenotyping which has great potential for highly multiplexed proteomic analysis. Expression of intracellular oncogenic kinase BCR/Abl, myeloid cell surface antigen CD33, human stem cell factor receptor c-Kit and integrin receptor VLA-4 were investigated using model human leukemia cell lines. Antigens to which specific antibodies are available and are distinguishably tagged can be determined simultaneously, or multiplexed. Four commercially available tags (Au, Sm, Eu, and Tb) conjugated to secondary antibodies enable a 4-plex assay assuming that the primary antibodies are not cross-reactive. Results obtained by ICP-MS were compared with data from FACS. ICP-MS as an analytical detector possesses several advantages that enhance the performance of immunoassays, which are discussed in detail. Although multiplexing using metal-conjugated reagents is in a very early stage of research and feasibility studies, it is already apparent that more than four antigens could be accurately detected simultaneously using the ICP-MS instrument.
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PMID:Multiple cellular antigen detection by ICP-MS. 1633 74

The concept of lymphoid differentiation in the human gastrointestinal tract is controversial but is the focus of this study, which examined adult human small intestinal tissue for the presence of CD34(+)CD45(+) hemopoietic stem cells (HSCs) and lymphoid progenitors. Flow cytometry demonstrated that over 5% of leukocytes (CD45(+) cells) isolated from human gut were HSCs coexpressing CD34, a significantly higher incidence than in matched peripheral blood or control bone marrow. HSCs were detected in cell preparations from both the epithelium and lamina propria of all samples tested and localized to the intestinal villous and crypt regions using immunofluorescence. A high proportion of gut HSCs expressed the activation marker CD45RA, and few expressed c-kit, indicating ongoing differentiation. The vast majority of intestinal HSCs coexpressed the T cell Ag, CD7 (92% in the epithelium, 80% in the lamina propria) whereas <10% coexpressed the myeloid Ag CD33, suggesting that gut HSCs are a relatively mature population committed to the lymphoid lineage. Interestingly, almost 50% of epithelial layer HSCs coexpressed CD56, the NK cell Ag, compared with only 10% of the lamina propria HSC population, suggesting that the epithelium may be a preferential site of NKR(+) lymphoid differentiation. In contrast, bone marrow HSCs displayed low coexpression of CD56 and CD7 but high coexpression of CD33. The phenotype of intestinal HSCs, which differs significantly from circulating or bone marrow HSCs, is consistent with a role in local lymphoid development.
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PMID:Detection and characterization of hemopoietic stem cells in the adult human small intestine. 1662 84

We have developed methods for detailed characterization of the proliferation kinetics and lineage potential of single human hematopoietic progenitor cells in an in vitro culture system. Fetal bone marrow CD34(hi)/lin(-) cells were cultured at one cell per well in the presence of c-kit ligand (KL), interleukin (IL)-3, IL-6, and leukemia inhibitory factor (LIF) on a murine stroma cell monolayer. Individual wells were scored for growth between 1 and 10 weeks of culture and analyzed by flow cytometry for lineage composition. A wide variation in time (1 to 8 weeks) was observed before initial cell division, even in the presence of cytokines promoting cell division in primitive progenitors. Eleven percent of the plated cells eventually produced a confluent culture well of approximately 20,000 progeny. Confluent wells were harvested and individually analyzed by flow cytometry for cell surface phenotype. Forty-eight percent of confluent wells contained primitive progenitors (CD34(+)lin(-)), 16% contained B-lymphoid cells (CD19(+) or CD10(+)), and 100% contained cells committed to the myelo-erythroid lineage (CD33(+)). CD34(+)/lin(-) cells from confluent wells were replated at one cell per well in secondary culture and the analysis repeated. One of 216 original single cells plated produced populations of B-lymphoid cells, myeloid cells, and primitive progenitors (CD34(+)/lin(-)) which persisted through two expansion cycles. We estimate that more than 36 million cells can be produced from a single cell under these culture conditions. A very small percentage of the CD34(hi)/lin(-) population (about 1%) was responsible for the majority of subsequent cell production. Our estimate of stem cell content in fetal bone marrow, defined by self-renewal as well as both B-lymphoid and myeloid differentiation from one cell, is approximately 1/13,000. This assay system provides direct in vitro measurements of the expected characteristics of hematopoietic stem cells (high proliferation potential, multilineage potential, self-renewal, and quiescence), and is therefore well suited to assessment of stem cell activity within various cell populations.
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PMID:In vitro characterization of fetal hematopoietic stem cells: range and kinetics of cell production from individual stem cells. 1862 9

Tumor immune tolerance can derive from the recruitment of suppressor cell populations, including myeloid-derived suppressor cells (MDSCs). In cancer patients, increased MDSCs correlate with more aggressive disease and a poor prognosis. Expression of 15 immune factors (TGFbeta, IL-1beta, IL-4, IL-6, IL-10, GM-CSF, M-CSF, IDO, fms-related tyrosine kinase 3 ligand, c-kit ligand, inducible NO synthase, arginase-1, TNF-alpha, cyclo-oxygenase 2, vascular endothelial growth factor [VEGF]) by MDSC-inducing human solid tumor cell lines was evaluated by RT-PCR. Based upon these data, cytokine mixtures were then tested for their ability to generate suppressive CD33(+) cells from healthy donor PBMCs in vitro by measuring their ability to inhibit the proliferation of, and IFN-gamma production by, fresh autologous human T cells after CD3/CD28 stimulation. Induced MDSCs were characterized with respect to their morphology, surface phenotype, and gene expression profile. MDSC-inducing cancer cell lines demonstrated multiple pathways for MDSC generation, including overexpression of IL-6, IL-1beta, cyclo-oxygenase 2, M-CSF, and IDO. CD33(+) cells with potent suppressive capacity were best generated in vitro by GM-CSF and IL-6, and secondarily by GM-CSF + IL-1beta, PGE(2), TNF-alpha, or VEGF. Characterization studies of cytokine-induced suppressive cells revealed CD33(+)CD11b(+)CD66b(+)HLA-DR(low)IL-13R alpha2(int) large mononuclear cells with abundant basophilic cytoplasm. Expression of inducible NO synthase, TGFbeta, NADPH oxidase, VEGF, and/or arginase-1 was also upregulated, and Transwell studies showed suppression of autologous T cells to be contact dependent. Suppressive CD33(+) cells generated from PBMCs by GM-CSF and IL-6 were consistent with human MDSCs. This study suggests that these cytokines are potential therapeutic targets for the inhibition of MDSC induction in cancer patients.
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PMID:Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. 2064 62

The most primitive hematopoietic stem cell (HSC)/progenitor cell (PC) population reported to date is characterized as being Lin-CD34+CD38-CD90+CD45R. We have a long-standing interest in comparing the characteristics of hematopoietic progenitor cell populations enriched from normal subjects and patients with chronic myelogenous leukemia (CML). In order to investigate further purification of HSCs and for potential targetable differences between the very primitive normal and CML stem/PCs, we have phenotypically compared the normal and CML Lin-CD34+CD38-CD90+CD45RA- HSC/PC populations. The additional antigens analyzed were HLA-DR, the receptor tyrosine kinases c-kit and Tie2, the interleukin-3 cytokine receptor, CD33 and the activation antigen CD69, the latter of which was recently reported to be selectively elevated in cell lines expressing the Bcr-Abl tyrosine kinase. Notably, we found a strikingly low percentage of cells from the HSC/PC sub-population isolated from CML patients that were found to express the c-kit receptor (<1%) compared with the percentages of HSC/PCs expressing the c-kitR isolated from umbilical cord blood (50%) and mobilized peripheral blood (10%). Surprisingly, Tie2 receptor expression within the HSC/PC subset was extremely low from both normal and CML samples. Using in vivo transplantation studies, we provide evidence that HLA-DR, c-kitR, Tie2 and IL-3R may not be suitable markers for further partitioning of HSCs from the Lin-CD34+CD38-CD90+CD45RA- sub-population.
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PMID:Further phenotypic characterization of the primitive lineage- CD34+CD38-CD90+CD45RA- hematopoietic stem cell/progenitor cell sub-population isolated from cord blood, mobilized peripheral blood and patients with chronic myelogenous leukemia. 2282 97

The purpose of this study was to evaluate the influence of bone marrow-mesenchymal stem cells (BM-MSC) and exogenously added cytokines on the proliferation, primitive cell subpopulation maintenance (including the c-kit+ marker) and clonogenic capacity of hematopoietic stem cells (HSC). BM-MSC were collected from volunteer donors, isolated and characterized. Umbilical cord blood (UCB) samples were collected from healthy full-term deliveries. UCB-CD34+ cells were cultured in the presence or absence of BM-MSC and/or cytokines for 3 and 7 days. CD34+ cell proliferation was evaluated using the CSFE method and cell phenotype was determined by CD34, c-kit, CD33, CD38, HLA-DR, cyCD22 and cyCD3 detection. Cell clonogenic ability was also assessed. Exogenously added SCF, TPO and FLT3L increased CD34+ cell proliferation in the presence or absence of BM-MSC, but with concomitant cell differentiation. Without any added cytokines, BM-MSC are able to increase the percentage of primitive progenitors as evaluated by c-kit expression and CFU-GEMM increase. Interestingly, this latter effect was dependent on both cell-cell interactions and secreted factors. A 7-day co-culture period will be optimal for obtaining an increased primitive HSC level. Including c-kit as a marker for primitive phenotype evaluation has shown the relevance of BM-MSC and their secreted factors on UCB-HSC stemness function. This effect could be dissociated from that of the addition of exogenous cytokines, which induced cellular differentiation instead.
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PMID:Mesenchymal stem cells promote a primitive phenotype CD34+c-kit+ in human cord blood-derived hematopoietic stem cells during ex vivo expansion. 2310 53


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