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)

Multiparameter flow cytometry was applied on normal human bone marrow (BM) cells to study the lineage commitment of progenitor cells ie, CD34+ cells. Lineage commitment of the CD34+ cells into the erythroid lineage was assessed by the coexpression of high levels of the CD71 antigen, the myeloid lineage by coexpression of the CD33 antigen and the B-lymphoid lineage by the CD10 antigen. Three color immunofluorescence experiments showed that all CD34+ BM cells that expressed the CD71, CD33, and CD10 antigens, concurrently stained brightly with anti-CD38 monoclonal antibodies (MoAbs). In addition, the CD38 antigen was brightly expressed on early T lymphocytes in human thymus, characterized by CD34, CD5, and CD7 expression. Only 1% of the CD34+ cells, 0.01% of nucleated cells in normal BM, did not express the CD38 antigen. The CD34+, CD38- cell population lacked differentiation markers and were homogeneous primitive blast cells by morphology. In contrast the CD34+, CD38 bright cell populations were heterogeneous in morphology and contained myeloblasts and erythroblasts, as well as lymphoblasts. These features are in agreement with properties expected from putative pluripotent hematopoietic stem cells; indeed, the CD34 antigen density decreased concurrently with increasing CD38 antigen density suggesting an upregulation of the CD38 antigen on differentiation of the CD34+ cells. Further evidence for a strong enrichment of early hematopoietic precursors in the CD34+, CD38- cell fraction was obtained from culture experiments in which CD34+ cell fractions with increasing density of the CD38 antigen were sorted singularly and assayed for blast colony formation. On day 14 of incubation, interleukin-3 (IL-3), IL-6, and GM-CSF, G-CSF, and erythropoietin (Epo) were added in each well. Twenty-five percent of the single sorted cells that expressed CD34 but lacked CD38 antigen gave rise to primitive colonies 28 to 34 days after cell sorting. The ability to form primitive colonies decreased rapidly with increasing density of the CD38 antigen. During 120 days of culture, up to five sequential generations of colonies were obtained after replating of the first-generation primitive colonies. This study provides direct evidence for the existence of a single class of progenitors with extensive proliferative capacity in human BM and provides an experimental approach for their purification, manipulation, and further characterization.
 ...
PMID:Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells. 170 33

We studied the effects of interleukin-4 (IL-4) and IL-6 on the growth of leukemic blasts from 40 patients with acute myelogenous leukemia (AML). Patients were selected on the basis of negativity for a series of B-cell antigens including CD10 and CD19. Twenty-one cases were CD34-positive (CD34+) (greater than 15% of blasts) and the remaining 19 were CD34-negative (CD34-) (less than 3% of blasts). IL-4 alone (100 U/ml) could stimulate either DNA synthesis (with greater than 2.0 stimulation index) or leukemic blast colony formation in 24 of 40 AML patients. In the presence of other growth factors, IL-4 showed divergent effects on IL-3-, granulocyte-macrophage colony-stimulating factor-, granulocyte colony-stimulating factor-, or erythropoietin-dependent colony formation. These effects of IL-4 were observed in both CD34+ and CD34- AML cases. IL-6 (100 U/mL) alone could not stimulate DNA synthesis and blast colony formation except for one CD34+ case. On the other hand, IL-6 showed synergistic effects on IL-3- and IL-4-dependent blast colony formation in 10 of 12 and 7 of 9 CD34+ AML cases, respectively. Among CD34- AML cases, such synergism was seen only in 1 of 12 cases for IL-3-dependent colony formation and in 3 of 7 cases for IL-4-dependent colony formation. The divergent effect of IL-4 and the synergistic effect of IL-6 were also observed in purified CD34+ leukemic blast populations, indicating that these phenomena are not mediated by accessory cells. The present study suggests that IL-4, alone or in combination with other growth factors, has divergent effects on the growth of AML progenitors irrespective of the CD34 expression, and that IL-6 acts synergistically with IL-3 or IL-4 on the growth of leukemic progenitors preferentially in CD34+ AML.
 ...
PMID:Effects of interleukin-4 and interleukin-6 on the proliferation of CD34+ and CD34- blasts from acute myelogenous leukemia. 171 40

A novel erythroid cell line, RM10, was established from a long-term bone marrow culture of a patient with chronic myelogenous leukemia (CML). RM10 cells were positive for periodic acid Schiff (PAS), but negative for peroxidase and dual esterase. RM10 cells had la, pre B (CD10), myeloid (CD13, CD14, CD33) and erythroid (glycophorin A) markers, but had no other lymphoid, megakaryocytic, or mesenchymal cell markers. RM10 cells spontaneously synthesized hemoglobin, which was markedly enhanced with hemin. Isoelectric focusing of the cell lysates and northern blot analysis of the total cellular RNA revealed hemoglobin synthesis in the cells. Using 125I-labeled recombinant human erythropoietin (Epo), two classes of Epo receptors were demonstrated in the RM10 cells. However, Epo did affect neither growth nor erythroid differentiation of the cells. RM10 cells rapidly differentiated to monocytic cells in the presence of 12-0-tetradecanoylphorbol-13-acetate, and simultaneously expressed glycoprotein IIb/IIIa. RM10 cells had Philadelphia chromosome (Ph), and expressed p210bcr-abl using immunoprecipitation with anti-c-abl and anti-phosphotyrosine antibodies. These results indicate that the RM10 cells have the characteristics of multipotential hemopoietic cells originating from Ph-positive CML and that high affinity Epo receptor class is not a sufficient condition for Epo responsiveness.
 ...
PMID:A novel CD10-positive erythroid cell line, RM10, established from a patient with chronic myelogenous leukemia. 216 10

Single- and multicolor flow cytometry were used to define progenitor subsets in normal human bone marrow and peripheral blood, cord blood, and blood following mobilization of CD34+ progenitor cells by cyclophosphamide or cyclophosphamide/etoposide/G-CSF treatment. CD34 cells were quantitated and subsets of CD34+ cells were defined by coexpression of CD33, CD13, CD10, CD19, CD45RA, and CD71. Myeloid and erythroid progenitors were quantitated by sorting single CD34+ cells into individual wells of 96-well plates containing methylcellulose, IL-3, GM-CSF, G-CSF, IL-6, and erythropoietin. Comparative studies of CD34 cells showed that the percentage of CD34+ mononuclear cells was greatest in blood samples from patients following mobilization treatment with cyclophosphamide/etoposide/G-CSF averaging 2%. By comparison, the remaining sample groups ranged from 1.68 to 0.15% CD34 cells in this order, bone marrow > cord blood > cyclophosphamide mobilized blood > peripheral blood. Comparison of CD34 cells per milliliter of bone marrow or blood showed a range of 22.4 x 10(4) to 0.65 x 10(4)/ml in the following order, bone marrow > chemotherapy/etoposide/G-CSF > cord blood > cyclophosphamide-mobilized blood. Comparative analysis of CD34 subsets from different sources showed significant differences, particularly bone marrow and blood samples. A distinct population of CD34+ CD19+ (Leu 12) CD10+ (CALLA) pre-B lymphocyte cells was defined in bone marrow with lower side and forward light scatter characteristics and was variable between donors (29.8 +/- 16.9%, mean +/- 1 SD; range, 3-54%; n = 8). This population was not found to a significant degree in blood and also expressed CD45RA (Leu 18). Coexpression studies of CD45RA and CD71 (transferrin receptor) expression on CD34+ cells defined a CD45RA- CD71+ population containing 89 +/- 6.3% (n = 4) BFU-E and a CD45RA+ CD71+ population that contained all CFU-GM (n = 4). LeuM7 (CD13) stained a larger percentage to a greater intensity than MY7 (CD13). Coexpression of CD45RA (Leu 18) and CD13 (LeuM7) defined a subset of CD13+ CD45RA+ cells enriched for CFU-GM and CFU-M with a cloning efficiency of 31%. Coexpression of CD33 (MY9) and CD13 (MY7) defined a population that was predominantly CFU-GM with a cloning efficiency of 38%. These studies define CD34+ phenotypes containing pure populations of B lymphocyte, granulocyte-macrophage, or erythroid progenitors and demonstrate the utility of multiparameter flow cytometry to define lineage-committed CD34+ cells.
 ...
PMID:Phenotypic analysis and characterization of CD34+ cells from normal human bone marrow, cord blood, peripheral blood, and mobilized peripheral blood from patients undergoing autologous stem cell transplantation. 750 11

A 75-year-old man developed a cluster of differentiation (CD)4-positive but human T-cell lymphotropic virus type I (HTLV-I)-negative T lymphoid neoplasm with overwhelming cutaneous involvement and mild thrombocytosis. Twelve courses tetrahydropyranyl adriamycin, cyclophosphamide, vincristine and prednisone (THP-COP) combination chemotherapy led him to complete remission. After four months of complete remission, however, atypical immature cells (blasts) appeared in peripheral blood and bone marrow. Surface marker analysis revealed the blasts to be CD2-, CD3-, CD4-, CD5-, CD7+, CD8-, CD10, CD13 +/-, CD19-, CD20-, CD25-, CD33+ and human leukocyte antigen-DR (HLA-DR+). Staining for myeloperoxidase, esterases, PAS and platelet peroxidase were all negative. The patient was diagnosed as having both CD7 and CD33 positive acute myeloid leukemia (AML). The relation between the T cell lymphoid neoplasm and AML was not clear. Thrombocytosis became more marked after acute leukemia occurred and the platelet count varied in parallel with the blast cell count in peripheral blood. When the leukemic cell count was high, thrombopoietic activity could be detected in the serum. In addition, conditioned medium obtained from primarily-cultured blasts had detectable thrombopoietic activity, which implied the blasts directly to produce a thrombopoietic factor(s). Analysis of the serum concentration for cytokines with associated thrombopoietic activity indicated that the blasts possibly produced a thrombopoietic factor(s) distinct from interleukin (IL)6, IL3, leukemia inhibitory factor (LIF), erythropoietin and granulocyte macrophage-colony stimulating factor. To our knowledge, this is the first reported case of an acute myeloid leukemia with marked thrombopoiesis (more than 2000 x 10(3)/microliter of maximum platelet count in peripheral blood.
 ...
PMID:Acute myeloid leukemia possibly producing thrombopoietic factor(s). 750 2

Erythropoietin is a growth factor. Cancer can be described as disturbance of the fine balance of positive and negative growth control mechanisms. The effect of human recombinant erythropoietin (EPO) was studied on the cell growth and differentiation of a human neuroblastoma cell line (h-NMB). Cell growth curves, trypan blue staining and thymidine uptake were used to assess cell proliferation and death. To assess cell differentiation, neutral endopeptidase (cell membrane enzyme marker), creatine kinase (cytosolic enzyme marker), dopamine uptake (dopamine transporter marker) and cell morphology were determined. Specific EPO receptor mRNA, by RT-PCR technique, was demonstrated. The incubation of erythropoietin with the tumor cell line resulted in inhibition of cell proliferation as evidenced in a diminished cell growth. EPO was shown to have induced a differentiation process as seen from the two different enzymatic markers, membranal and cytosolic, and from the cells dopamine uptake studies. However, the morphological changes did not document a full differentiation effect. EPO specific antibodies blocked the effects of EPO on cell proliferation and creatine kinase activity. In this study, EPO did not produce any sign of proliferation in the nervous tumor cell line used.
 ...
PMID:The effect of human recombinant erythropoietin on the growth of a human neuroblastoma cell line. 876 Oct 3

Mesenchymal stem cells (MSCs) can ameliorate symptoms in several neurodegenerative diseases. However, the toxic environment of a degenerating central nervous system (CNS) characterized by hypoxia, glutamate (Glu) excess and amyloid beta (Abeta) pathology may hamper the survival and regenerative/replacing capacities of engrafted stem cells. Indeed, human MSC (hMSC) exposed to hypoxia were disabled in (i) the capacity of their muscarinic receptors (mAChRs) to respond to acetylcholine (ACh) with a transient increase in intracellular [Ca(2+)], (ii) their capacity to metabolize Glu, reflected by a strong decrease in glutamine synthetase activity, and (iii) their survival on exposure to Glu. Cocultivation of MSC with PC12 cells expressing the amyloid precursor protein gene (APPsw-PC12) increased the release of IL-6 from MSC. HMSC exposed to erythropoietin (EPO) showed a cholinergic neuron-like phenotype reflected by increased cellular levels of choline acetyltransferase, ACh and mAChR. All their functional deficits observed under hypoxia, Glu exposure and APPsw-PC12 cocultivation were reversed by the application of EPO, which increased the expression of Wnt3a. EPO also enhanced the metabolism of Abeta in MSC by increasing their neprilysin content. Our data show that cholinergic neuron-like differentiation of MSC, their functionality and resistance to a neurotoxic environment is regulated and can be improved by EPO, highlighting its potential for optimizing cellular therapies of the CNS.
 ...
PMID:Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin. 1960 78

The upstream regulatory sequence (URS), NF1 region, enhancer, promoter, 1st exon, and intron A of human cytomegalovirus major immediate early gene (hCMV MIE) are evaluated for enhancing transient and stable gene expression levels in two industrial cell lines, CHO K1 and HEK293 using firefly luciferase (Fluc) and erythropoietin (EPO). As compared to the control vector which only contains the enhancer and promoter (EP), vectors containing the 1st exon (EPE) and intron A (EPEI) enhance transient expression levels of the two proteins by approximately 2.5- to 4.3-fold in the two cell lines. Addition of NF1 and URS to EP (NEP and UNEP) or EPEI (NEPEI and UNEPEI) results in a lesser effect on the expression. In stable transfections, UNEPEI provides the highest expression level in CHO K1 cells, yielding approximately 4.0-fold increase in Fluc expression and 2.5-fold increase in EPO expression. In HEK293 cells, EPE is the best and enhances Fluc and EPO expression by more than 2.0-fold. Such information is valuable for the development of optimal vectors to enhance transient and stable production of recombinant proteins in CHO K1 and HEK293 cells.
 ...
PMID:Evaluating regulatory elements of human cytomegalovirus major immediate early gene for enhancing transgene expression levels in CHO K1 and HEK293 cells. 2041 45