Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case is reported of an adult male patient with acute leukemia characterized by the presence of the novel cytogenetic abnormality, t(2;9)(p12;p23), in addition to a t(4;11)(q21;q23). The immunophenotype of the blast cell population was consistent with immature early pre-B cell acute lymphoblastic leukemia (ALL) (TdT+,HLA-DR+,CD19+,CD24 +/-,CD10-) expressing myelo-monocytic antigens (CDw65,CD15). The genotype showed a clonal rearrangement of the immunoglobulin heavy chain locus. Because the immunoglobulin kappa (kappa) light chain gene is located on chromosome 2 at band p12 and interferon alpha (alpha) and beta (beta) map to chromosome 9p21-p22, rearrangements of these loci as a result of the t(2;9) were studied. There was no evidence for rearrangement of the region covering about 40 kilobases around the kappa locus when hybridized to C(kappa), the 3' kappa enhancer or the kappa deleting element. Only germline size restriction fragments were also found for the interferon alpha and beta genes. The patient's clinical features were typical for ALL associated with the t(4;11), including a high white blood cell count at presentation, hepatosplenomegaly, and a poor outcome. The potential significance of 2p and 9p abnormalities in addition to t(4;11) is discussed.
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PMID:Translocation (2;9)(p12;p23) in a case of acute leukemia with t(4;11)(q21;q23). Lack of rearrangement of the kappa and interferon gene loci. 137 31

This study is intended to establish biological correlation between the expression of lymphoid associated features in acute myeloid leukaemia (AML). In 62 AML patients, predominantly enrolled on Eastern Cooperative Oncology Group (ECOG) treatment protocols, in whom immunoglobulin (Ig) as well as T-cell receptor beta chain (TCR-beta) gene rearrangement analyses had been performed, morphology, cytochemistry, antigen profile and karyotype were reviewed retrospectively. Nuclear reactivity with anti-TdT antibody was demonstrated in 34 patients (55%) and confirmed by ribonuclease protection assay in all patients tested. Five TdT-protein negative patients were TdT-transcript positive. Lymphoid antigens (lyA) were detected in 24 of 51 cases tested (47%) with B-cell antigens (CD19, CD10) being restricted to TdT+ AML (P = 0.03). Only two patients had Ig heavy, none had Ig light chain or TCR-beta gene rearrangements. Although both patients with rearranged Ig loci were TdT+, either by protein or RNA analysis, the low incidence of such rearrangement within the TdT+ AML group (6%) argues against a significant association between the presence of TdT and crosslineage Ig gene rearrangements in AML. While FAB-diagnoses did not differ between TdT+ and TdT- or lyA+ and lyA- AML, particular immunophenotypic features correlated with TdT positively, e.g. the presence of early antigens, CD34 and HLA-DR, and the absence of the more mature myelo-monocytic antigens, CDw65 and CD14. Certain cytogenetic abnormalities were associated with TdT+ AML such as inv(16) (p13q22) or t(16;16) (p12;q22) (five patients; P = 0.03) and t(8;21) (q22;q22) (three patients). A greater number of TdT- than TdT+ AML patients had only normal karyotypes (P = 0.06). Neither immunophenotypic nor karyotypic correlations could be established for lyA+ AML.
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PMID:Lymphoid lineage-associated features in acute myeloid leukaemia: phenotypic and genotypic correlations. 141 14

The receptor for urokinase-type plasminogen activator (uPA-R) localizes uPA to the cell surface. The receptor-bound uPA converts plasminogen to the trypsin-like endopeptidase plasmin. Thus uPA is involved in the initiation of pericellular proteolysis. Pericellular proteolysis is assumed to facilitate the cellular infiltration into surrounding tissue. The uPA-R has recently been identified as a surface antigen of activated human T lymphocytes. We have characterized the uPA-R of the human CD4 T cell line Jurkat by immunological (flow cytometry), biochemical (ligand blotting), and physico-chemical (Scatchard blotting) methods. The collective data suggest that the human CD4+ T cell line Jurkat expresses a cell surface receptor for uPA similar to that of myelo/monocytes and normal T cells with regard to size, affinity, ligand specificity, and antigenicity. Binding studies using exogenous uPA and subsequent functional assays revealed that receptor-bound uPA retains its enzymatic activity. Saturation of the Jurkat cell uPA-R with exogenous uPA facilitated cellular invasion into fibrin matrices in vitro. uPA-dependent invasion was inhibited in the presence of an anti-catalytic monoclonal anti-uPA antibody. We propose that uPA-R-bound uPA may facilitate the invasiveness of uPA-R-positive T lymphocytes.
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PMID:Urokinase-type plasminogen activator enhances invasion of human T cells (Jurkat) into a fibrin matrix. 791 95

The class III receptor tyrosine kinase FLT3/FLK2 (FLT3; CD135) represents an important molecule involved in early steps of hematopoiesis. Here we compare cell-surface expression of FLT3 on bone marrow (BM) and cord blood (CB) cells using monoclonal antibodies (MoAbs) specific for the extracellular domain of human FLT3. Flow cytometric analysis of MACS-purified BM and CB cells showed that 63% to 82% of BM CD34+ and 88% to 95% of the CB CD34+ cells coexpress FLT3. Clonogenic assays and morphological characterization of FACS-sorted BM CD34+ cells demonstrate that colony-forming unit-granulocyte-macrophage (CFU-GM) and immature myelo-monocytic precursor cells are enriched in the subpopulation staining most brightly with the FLT3 MoAb whereas the majority of the burst-forming units-erythroid (BTU-E) and small cells with lymphoid morphology are found in the FLT3- population. In contrast, statistically indistinguishable proportions of CFU-granulocyte-erythrocyte-megakaryocyte-macrophage (CFU-GEMM) and more primitive cobblestone area forming cells (CAFC) were detected in both fractions, albeit the FLT3+ fraction consistently showed more CAFC activity than the FLT3- fraction. Although in both, BM and CB the majority of CD34+CD117+ (KIT+), CD34+CD90+ (Thy-1+), and CD34+CD109+ cells coexpress FLT3, three-color phenotypic analyses are consistent with the functional findings and suggest that the most primitive cells defined as CD34+CD38-, CD34+CD71low, CD34+HLA-DR-, CD34+CD117low, CD34+CD90+, and CD34+CD109+ express low levels of cell-surface FLT3 and were therefore not enriched to a statistically significant extent with the bright versus negative sorting scheme. Thus, clear segregation of the most primitive progenitors from BM CD34+ cells was confounded by low apparent levels of FLT3 cell-surface expression on these cells, whereas myeloid progenitors unambiguously segregated with the FLT3 brightest cells and erythroid progenitors with the FLT3 dimmest. Additional phenotypic analyses using MoAbs against progenitor/stem cell markers including the mucinlike molecule MGC-24v (CD164), the receptor tyrosine kinases TIE, FMS (CD115), and KIT (CD117) further illustrate the differences in surface antigen expression profiles of BM and CB CD34+ cells. Notably, CD115 is rarely detected on CB CD34+ cells, whereas 20% to 25% of the BM CD34+FLT3+ cells are CD115+. Furthermore, 80% to 95% of the CB CD34+CD117+ but only 60% to 75% of the BM CD34+CD117+ cells coexpress FLT3. Only a negligible amount of CD34+CD19+ are detected in CB, while in BM 20% to 30% of CD34+CD19+ presumed pro/pre-B cells coexpress FLT3. In contrast, the majority of the CD34+CD164+ and CD34+TIE+ subsets in both CB and BM coexpress FLT3. Analysis of unseparated cells showed that FLT3 expression is not restricted to CD34+ subsets. About 65% to 70% of lymphocyte-gated BM CD34-FLT3+ cells are positive for the monocytic marker CD115 whereas 25% to 30% of these cells consist of CD10 expressing B-cell precursors. Finally, CD34- monocytes in BM, CB, and PB express FLT3 whereas granulocytes are FLT3-. Our data show that detectable FLT3 appears first at low levels on the surface of primitive multilineage progenitor cells and disappears during defined stages of B-cell development, but is upregulated and maintained during monocytic maturation.
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PMID:Functional and phenotypic characterization of cord blood and bone marrow subsets expressing FLT3 (CD135) receptor tyrosine kinase. 920 45

The identity and lineage potential of the cells that initiate thymopoiesis remain controversial. The goal of these studies was to determine, at a clonal level, the immunophenotype and differentiation pathways of the earliest progenitors in human thymus. Although the majority of human CD34(+)lin(-) thymocytes express high levels of CD7, closer analysis reveals that a continuum of CD7 expression exists, and 1% to 2% of progenitors are CD7(-). CD34(+)lin(-) thymocytes were fractionated by CD7 expression and tested for lineage potential in B-lymphoid, T-lymphoid, and myeloid-erythroid conditions. Progressive restriction in lineage potential correlated with CD7 expression, that is, the CD7(hi) fraction produced T and NK cells but lacked B and myelo-erythroid potential, the CD7(int) (CD10(+)) fraction produced B, T, and NK cells, but lacked myelo-erythroid potential. The CD7(-) fraction produced all lymphoid and myelo-erythroid lineages and expressed HSC-associated genes. However, CD34(+)lin(-)CD7(-) thymocytes also expressed early T lymphoid genes Tdt, pTalpha, and IL-7Ralpha and lacked engraftment capacity, suggesting the signals that direct lymphoid commitment and corresponding loss of HSC function are rapidly initiated on arrival of HSC in the human thymus. Thus, differential levels of CD7 identify the progressive stages of lineage commitment in human thymus, initiated from a primitive CD7(-) lympho-myeloid thymic progenitor.
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PMID:Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7- lympho-myeloid thymic progenitors. 1795 57

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