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 earliest T cells homing to the thymus (CD3-CD4loCD8-) express CD117 (c-kit), CD43 (leukosialin), and the integrins CD11a (alphaL), CD11b (alphaM), CD29 (beta1), CD49f (alpha6), and CD44. Using reagents specific for CD44 variant isoforms (CD44v), we demonstrated that CD44v were expressed on virtually all early thymocytes,whereas cells carrying only the standard molecule (CD44s, not containing any variant domains), which is ubiquitously found on mature lymphocytes later, are very sparse. The expression of CD44v was closely correlated with CD43 and CD117 and was restricted to the CD3-CD4loCD8- stage. CD44v were detected on lymphocyte progenitor populations in the fetal blood, liver, thymus and spleen, as well as in the adult bone marrow. Functional studies demonstrated that only cells expressing CD44v from fetal liver and adult bone marrow could efficiently populate fetal thymic stroma and develop into mature T cells. In fetal thymic organ cultures anti-CD44v antibodies specifically blocked thymocyte development. We also present evidence that CD44v were required for the initial interaction of hematopoietic progenitor cells with the thymic stroma. Our data imply that CD44v are not only a useful marker for hematopoietic progenitors, but also play a functional role in the initiation of thymocyte development.
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PMID:Variant isoforms of CD44 are required in early thymocyte development. 1159 76

The true identity of Hodgkin's mononuclear cells and Reed-Sternberg (H-RS) cells has been a subject of controversy for decades. Those who believe that Hodgkin's disease (HD) is a heterogeneous disease may consider it to constitute lymphomas of various origins. However, this theory seems incompatible with the finding of similar phenotypic, biologic, and immunologic properties among most HD. We believe that, in the majority of cases, HD, except for LP and some LD-type HD, is a homogeneous disease despite differences in the degree of fibrosis and/or cellular reaction. The heterogeneity in cellular reactions is a result of secretion of various cytokines by H-RS cells, which may or may not be influenced by the presence of EBV. H-RS cells, and anaplastic large cell lymphoma (ALCL) cells as well, can express a combination of cytokines and cytokine receptors that is not seen in other types of lymphomas. The unique cytokine/receptor profile (e.g. the expression of c-kit-R/CD117), along with various properties associated with H-RS/ALCL cells, leads to a hypothesis that H-RS/ALCL cells are related to similar lymphohematopoietic progenitor cells with different etiologies and somewhat limited differentiation capacity. A number of H-RS cells may differentiate with limited capacity along the B-cell pathway and may be infected by EBV, which further complicates the biologic and immunologic properties of these cells. The majority of H-RS cells may also, however, differentiate along the antigen-presenting dendritic cell pathway, as indicated by the abundant expression of restin, CD15, CD40, CD54, CD58, CD80, and CD86. The majority of ALCL cells clearly differentiate to T cells, but some may acquire B-cell or histiocyte phenotypes. The progenitor cell hypothesis may explain (1) the variable expression of CD117, CD43, and CD34 as well as the absence of CD27, CD45 and CD45RA in H-RS cells; (2) the inconsistent and irregular patterns of phenotype and genotype and the various, often very limited, degrees of differentiation among these two types of lymphoma cells; (3) the existence of secondary HD or ALCL associated with rare types of lymphomas or leukemias, or vice versa; (4) the absence of recombinase and of the B-specific transcription factors BSAP; and (5) the frequent expression of IL-7 and IL-9 in H-RS cells. Copyright 1996 S. Karger AG, Basel
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PMID:Hodgkin's Disease and Anaplastic Large Cell Lymphoma Revisited. ii. from cytokines to cell lineage. 1172 77

Recent studies have demonstrated that lineage marker-negative (Lin(-)) c-kit(Lo) Flk-2/Flt3(+) IL-7R(+) Sca-1(Lo) CD27(+) Ly-6C(-) Thy-1(-)CD43(+) CD16/32(Lo/-) terminal deoxynucleotidyl transferase (TdT)(+) cells in murine bone marrow are functional lymphocyte precursors. However, it has not been clear if this is an obligate intermediate step for transit of multipotential hematopoietic stem cells to natural killer (NK) cells. We have now used serum-free, stromal cell-free cultures to determine that NK progenitors are enriched among an estrogen-regulated, c-kit(Lo) subset of the Lin(-) fraction. However, several experimental approaches suggested that this population is heterogeneous and likely represents a stage where B and NK lineages diverge. Although most B-cell precursors were directly sensitive to estrogen in culture, much of the NK-cell precursor activity in that fraction was hormone resistant. B-lineage potential was largely associated with interleukin 7 receptor alpha (IL-7R(alpha)) expression and was selectively driven in culture by IL-7. In contrast, many NK precursors did not display detectable amounts of this receptor and their maturation was selectively supported by IL-15. Finally, single-cell experiments showed that the Lin(-) c-kit(Lo) fraction contains a mixture of B/NK, B-restricted, and NK-restricted progenitors. Two-step culture experiments revealed that NK precursors become hormone resistant on or before acquisition of CD122, signaling commitment to the NK lineage. CD45R is preferentially, but not exclusively, expressed on maturing B-lineage cells. Production of these 2 blood cell types is regulated in bone marrow by common and then independent mechanisms that can now be studied with greater precision.
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PMID:Relationships between early B- and NK-lineage lymphocyte precursors in bone marrow. 1239 56

Our laboratory recently identified a quiescent class of pluripotent hematopoietic stem cells (PHSCs) that are lineage negative (Linneg), lack c-Kit, and are able to give rise to c-Kit-positive (c-Kitpos) PHSCs in vivo. This population fails to proliferate in vitro but has delayed reconstituting activity in vivo. In this study, we purified these cells to enrich for the PHSCs and we identified in vitro conditions capable of supporting their maturation. The c-Kit-negative (c-Kitneg) cells exhibited differential expression of Sca-1, CD34, CD43, CD45, and Thy 1.2. We purified the cells based on Sca-1, as it is expressed on active PHSCs. We detected pre-colony-forming unit spleen (pre-CFU-s) activity in both the Sca-1neg and Sca-1pos populations, indicating the presence of primitive PHSCs in both populations. However, our in vitro studies suggest that the Sca-1pos population is enriched for PHSCs. The in vitro systems that support the growth of these dormant cells include a modified long-term marrow culture and various stromal cell lines. In modified long-term bone marrow cultures, c-Kitneg cells gave rise to c-Kitpos PHSCs, with long-term reconstitution activity in vivo. Thus we have established an in vitro system to examine PHSC maturation that will allow us to study the mediators of the c-Kitneg to c-Kitpos transition.
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PMID:Identification of in vitro growth conditions for c-Kit-negative hematopoietic stem cells. 1285 62

Emerging evidence indicates that Notch receptors and their ligands play important roles in the development of T cells and B cells. However, little is known about their possible roles in the development of other lymphoid cells. Here we demonstrate that Jagged2, a Notch ligand, stimulates the development of natural killer (NK) cells from Lin(-) Sca-1(+) c-kit(+) hematopoietic stem cells. Our culture system supports NK cell development for 2 to 3 months, often leading to the establishment of continuous NK cell lines. The prototype of such cell lines is designated as KIL. KIL depends on interleukin-7 for survival and proliferation and is NK1.1(+) CD3(-) TCRalphabeta(-) TCRdeltagamma(-) CD4(-) CD8(-) CD19(-) CD25(+) CD43(+) CD45(+) CD49b(-) CD51(+) CD94(+) NKG2D(+) Mac-1(-/low) B220(-) c-kit(+) perforin I(+) granzyme B(+) Notch-1(+), and cytotoxic. Like normal natural killer cells, the T-cell receptor-beta loci of KIL remain in the germ-line configuration. In response to interleukin-2, KIL proliferates extensively (increasing cell number by approximately 10(10)-fold) and terminally differentiates into adherent, hypergranular NK cells. Our findings indicate that Jagged2 stimulates the development of natural killer cells and the KIL cell line preserves most properties of the normal NK precursors. As such, KIL provides a valuable model system for NK cell research.
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PMID:Jagged2 promotes the development of natural killer cells and the establishment of functional natural killer cell lines. 1565 53

This report describes a rare case of an extramedullary myeloid tumour (EMMT) of the gallbladder in a patient without leukaemia. A 33 year old man visited a local hospital because of jaundice. Abdominal computed tomography revealed a tumorous mass measuring 6.0 x 4.5 cm and involving the entire gallbladder. A percutaneous needle biopsy was attempted, but because adenocarcinoma could not be completely ruled out, the use of undue force was considered dangerous. Under a preoperative diagnosis of gallbladder carcinoma, a hepatopancreatoduodenectomy was performed. The tumour cells exhibited various amounts of eosinophilic cytoplasm, had medium sized round nuclei with indentation and grooving, and were strongly immunoreactive for myeloperoxidase, CD43, and c-kit protein (CD117). After surgery, the patient underwent combination chemotherapy as prescribed for cases of acute myeloblastic leukaemia. The patient did not develop acute leukaemia during a follow up period of four years. In conclusion, a correct diagnosis of EMMT can be made using appropriate immunohistochemical staining.
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PMID:Extramedullary myeloid tumour (EMMT) of the gallbladder. 1567 45

Plasmacytoid dendritic cells (pDCs) competent to make type I interferon were rigorously defined as a Ly-6C(+) and CD11c(Lo) subset of the B220(+)CD19(-) CD43(+)CD24(Lo) bone marrow (BM) Fraction A. Otherwise similar Ly6C(-) cells expressed the natural killer (NK) markers DX5 and NK1.1. pDCs represented a stable, discrete, and long-lived population. Stem cells and early lymphoid progenitors (ELPs), but not prolymphocytes, were effective precursors of pDCs, and their differentiation was blocked by ligation of Notch receptors. Furthermore, pDCs were present in the BM of RAG1(-/-), CD127/IL-7Ra(-/-), and Pax5(-/-) mice. pDCs in RAG1/GFP knock-in mice could be subdivided, and immunoglobulin D(H)-J(H) rearrangements, as well as transcripts for the B-lineage-related genes Pax5, mb1/CD79a, ebf, and Bcl11a, were identified only in the green fluorescent protein-positive (GFP(+)) pDC1 subset. All pDCs expressed terminal deoxynucleotidyl transferase (TdT), the ETS transcription factor Spi-B, the nuclear factor-kappaB transcription factor RelB, toll-like receptor 9 (TLR9), and interferon consensus sequence binding protein (ICSBP)/interferon regulatory factor 8 (IRF-8) transcripts; lacked CD16 and granulocyte colony-stimulating factor receptor (G-CSFR); and were uniformly interleukin-7 receptor alpha (IL-7Ralpha(-)) AA4.1(Lo), CD27(-), Flk-2(Lo), c-Kit(-), DX-5(-), and CD11b(-), while CD4 and CD8alpha were variable. GFP(+) pDC1 subset was less potent than GFP(-) pDC2s in T allostimulation and production of tumor necrosis factor alpha (TNFalpha), interferon alpha (IFNalpha), and interleukin-6 (IL-6), while only pDC2s made IFNgamma and IL-12 p70. Thus, 2 functionally specialized subsets of pDCs arise in bone marrow from progenitors that diverge from B, T, and NK lineages at an early stage.
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PMID:Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow. 1572 31

Rearrangements in reading frame 2 promote the expression of a truncated heavy chain, the Dmu protein. Dmu can assemble into a pre-B cell receptor like complex that appears to induce a subset of signals elicited by full length mu, but cannot promote the pro-B to pre-B cell transition of Rag-/- B cells. In order to determine if this could stem from an impaired survival signal not properly induced by the Dmu protein, we introduced Bcl-2 into Dmu-transgenic, Rag2-/- mice. Despite the fact that the Bcl-2 transgene expression promoted some increase in the fraction of CD43- B cells, an identical increase was also observed in Rag2-/- mice. Moreover, whereas in mu-transgenic Rag2-/-Bcl-2+ mice, CD2 and CD25 expression were up regulated and c-Kit was down regulated, these markers were unaltered in Dmu-transgenic Rag2-/- Bcl-2+ mice compared to Rag2-/- Bcl-2+ mice, indicating that Dmu cannot support pre-B cell maturation despite extended survival of B cell precursors by Bcl-2. In addition, we observed that in Dmu-transgenic recombination competent mice, the Dmu induced partial block is permissive for marginal zone B cell development whereas the formation of follicular B cells is severely reduced. While the Dmu protein is expressed in peripheral B cells escaping the block, only a minor fraction of Dmu is exposed to the outer cell surface.
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PMID:Dmu expression causes enrichment of MZ B cells, but is non permissive for B cell maturation in Rag2-/- mice even if combined with Bcl-2. 1632 40

This study was designed to investigate one component of the Wnt/beta-catenin signaling pathway that has been implicated in stem cell self-renewal. Retroviral-mediated introduction of stable beta-catenin to primitive murine bone marrow cells allowed the expansion of multipotential c-Kit(low)Sca-1(low/-)CD19(-) CD11b/Mac-1(-)Flk-2(-)CD43(+)AA4.1(+)NK1.1(-)CD3(-)CD11c(-)Gr-1(-)CD45R/B220(+) cells in the presence of stromal cells and cytokines. They generated myeloid, T, and B lineage lymphoid cells in culture, but had no T lymphopoietic potential when transplanted. Stem cell factor and IL-6 were found to be minimal requirements for long-term, stromal-free propagation, and a beta-catenin-transduced cell line was maintained for 5 mo with these defined conditions. Although multipotential and responsive to many normal stimuli in culture, it was unable to engraft several types of irradiated recipients. These findings support previous studies that have implicated the canonical Wnt pathway signaling in regulation of multipotent progenitors. In addition, we demonstrate how it may be experimentally manipulated to generate valuable cell lines.
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PMID:Constitutively active beta-catenin promotes expansion of multipotent hematopoietic progenitors in culture. 1688 90

We report a rare case of myeloid sarcoma (MS) of the extrahepatic bile ducts presenting as obstructive jaundice in a patient without leukemia at time of diagnosis. A 75-year-old female presented with a one-month history of abdominal pain and jaundice. Computerized tomography scan of the abdomen showed stenosis of the extrahepatic bile ducts. Endoscopic retrograde cholangiography disclosed an irregular narrowing of the common biliary duct, suggestive of a cholangiocarcinoma, and resection was performed. Histologic examination showed diffuse transmural infiltration of malignant cells. These cells exhibited medium-sized round nuclei with central nucleoli and eosinophilic cytoplasm, and were strongly positive for myeloperoxidase, CD68, lysozyme, CD45, CD117 (c-kit protein) and CD43. Eight months following surgery the patient presented with multiple cutaneous nodules and bone marrow trephine biopsy showed acute myelomonocytic leukemia. A literature search identified two previously reported cases of MS of the extrahepatic biliary duct. MS should be taken into consideration in the differential diagnosis of a patient with obstructive jaundice. Immunohistochemistry is essential for a correct diagnosis.
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PMID:Myeloid sarcoma of the extrahepatic bile ducts presenting as obstructive jaundice. 1694 23


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