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)

Immunomagnetic beads are well suited for positive selection of CD34+ cells. However, both unspecific binding of beads to cells as well as the effectiveness of detachment of beads from cells may represent significant problems. We used an anti-Fab antiserum (DETACHaBEAD, Dynal) for rapid and effective detachment of immunomagnetic beads from the positively selected cells. By this detachment technique, the cells remained phenotypically unaltered. To reduce unspecific binding, we have coated various anti-CD34 monoclonal antibodies directly to paramagnetic beads M450 (Dynal). Use of beads coated with BI-3C5 was found to be optimal with regard to yield and purity of the isolated cells. The yield was on average 1.5% (range 0.5-2.5%) of bone marrow mononuclear cells and the purity was usually greater than 95% CD34+ cells of the isolated cells. Subpopulations of the cells expressed myeloid markers (CD13, CD33, and to a lesser extent CD15 and CD14) or early B-lineage markers (CD19 and CD10). Most of the cells expressed CD38, and a majority of the cells also expressed CD41. In general, most of the CD34+ cells with low forward scatter expressed B-lineage markers, as was also the case for the few contaminating CD34- cells which were found to be predominantly CD37+ mature B cells. Reactivity with antibodies against T-lineage markers (CD2, CD3, CD4, CD7, and CD8) was generally detected only on 1-2% of the cells or less. Isolated cells responded to interleukin 3, granulocyte-macrophage colony-stimulating factor, mast cell growth factor, and/or granulocyte colony-stimulating factor alone or in combinations in short-term liquid cultures. The cells were also markedly enriched for granulocyte-macrophage colony-forming units as well as for early progenitor cells capable of forming blast colonies on preformed stromal feeder layers. Moreover, the CD34- population was depleted of 70-80% of CFU-GM and cells capable of blast colony formation. Thus, we conclude that the isolated cells are phenotypically unaltered after isolation, and show a normal response in various in vitro assays.
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PMID:Isolation and characterization of human hematopoietic progenitor cells: an effective method for positive selection of CD34+ cells. 137 14

Two novel cytokines, stem cell factor (SCF) and PIXY321 (a fusion protein, granulocyte macrophage colony-stimulating factor+IL-3), have recently been demonstrated to enhance in vitro adult myelopoiesis. In this study, we compared the success of separating very early hematopoietic progenitor cells (CD34+) from both cord blood (CB) and adult bone marrow (ABM) and their differential response to SCF, PIXY321, and other later-acting colony-stimulating factors (CSF). Briefly, CD34+ cells were isolated from CB and ABM with an anti-CD34 MAb, HPCA-1, and incubated with various combinations of SCF, PIXY321, and other CSF. The percentage of CD34+ cells was decreased in CB compared to ABM before separation (0.54 versus 1.71%) (p = 0.05). Isolated CD34+ cells from CB and ABM were similar in lineage with respect to CD38, HLA-DR, CD33, and CD5, but decreased in CB with respect to B-lineage expression (CD19, CD10, and CD22) (p = 0.05). SCF increased colony forming unit-granulocyte-macrophage (CFU-GM) formation from CB CD34+ cells compared to unconditioned media and had a significant additive increase with IL-3 (p = 0.006) and granulocyte colony-stimulating factor (p = 0.03). SCF also had an additive increase in CB CFU-GM formation with PIXY321 (p = 0.007). PIXY321 had a similar increase in CFU-GM formation from both CB and ABM CD34+ cells compared to the combination granulocyte macrophage colony-stimulating factor + IL-3. When SCF was added to IL-3, PIXY321, or PIXY321 + IL-6, there was an increase in CFU-GM from CB versus ABM CD34+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The in vitro effects of stem cell factor and PIXY321 on myeloid progenitor formation (CFU-GM) from immunomagnetic separated CD34+ cord blood. 138 18

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.
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PMID:Effects of interleukin-4 and interleukin-6 on the proliferation of CD34+ and CD34- blasts from acute myelogenous leukemia. 171 40

Peripheral blood (PB) CD34+ cells from four commonly used mobilization protocols were studied to compare their phenotype and proliferative capacity with steady-state PB or bone marrow (BM) CD34+ cells. Mobilized PB CD34+ cells were collected during hematopoietic recovery after myelosuppressive chemotherapy with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) or during G-CSF administration alone. The expression of activation and lineage-associated markers and c-kit gene product were studied by flow cytometry. Proliferative capacity was measured by generation of nascent myeloid progenitor cells (granulocyte-macrophage colony-stimulating factor; CFU-GM) and nucleated cells in a stroma-free liquid culture stimulated by a combination of six hematopoietic growth factors (interleukin-1 (IL-1), IL-3, IL-6, GM-CSF, G-CSF, and stem cell factor). G-CSF-mobilized CD34+ cells have the highest percentage of CD38- cells (P < .0081), but otherwise, CD34+ cells from different mobilization protocols were similar to one another in their phenotype and proliferative capacity. The spectrum of primitive and mature myeloid progenitors in mobilized PB CD34+ cells was similar to their steady-state counterparts, but the percentages of CD34+ cells expressing CD10 or CD19 were lower (P < .0028). Although steady-state PB and chemotherapy-mobilized CD34+ cells generated fewer CFU-GM at day 21 than G-CSF-mobilized and steady-state BM CD34+ cells (P < .0449), the generation of nucleated cells and CFU-GM were otherwise comparable. The presence of increased or comparable numbers of hematopoietic progenitors within PB collections with equivalent proliferative capacity to BM CD34+ cells is not unexpected given the rapid and complete hematopoietic reconstitution observed with mobilized PB. However, all four types of mobilized PB CD34+ cells are different from steady-state BM CD34+ cells in that they express less c-kit (P < .0002) and CD71 (P < .04) and retain less rhodamine 123 (P < .0001). These observations are novel and suggest that different mobilization protocols may act via similar pathways involving the down-regulation of c-kit and may be independent of cell-cycle status.
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PMID:A comparative study of the phenotype and proliferative capacity of peripheral blood (PB) CD34+ cells mobilized by four different protocols and those of steady-phase PB and bone marrow CD34+ cells. 752 60

Bone marrow (BM) is most frequently used to transplant hematopoietic progenitor cells, but umbilical cord blood (UCB) and mobilized peripheral blood (PB) provide alternative sources of progenitor cells for transplantation. To study whether the clonogenicity and phenotype of progenitor cells vary between the compartments, CD34+ cells from UCB, mobilized PB, and BM were analyzed for in vitro colony formation and characterized by immunophenotyping for several lineage-associated and maturation-related cell surface molecules. We found that circulating CD34+ cells, either from PB after granulocyte colony-stimulating factor (G-CSF) mobilization or from UCB, contained a large proportion of cells (86-96%) with myeloid cell-associated molecules (CD33 and CD13) and clonogenic cells (colony-forming unit-granulocyte-macrophage and burst-forming unit-erythrocyte) in excess of BM CD34+ cells. Further, UCB and PB CD34+ cells contained > or = 3% cells with a phenotype associated with immature (HLA-DR- and CD38-) progenitor cells, which was comparable to what is found among BM CD34+ cells. The proportion of CD34+ cells in UCB expressing the B cell-associated molecules (CD10 and CD19) was comparable to that found in mobilized PB (< or = 5%) but significantly lower than for BM CD34+ cells (19-24%). Further, we observed a higher proportion of CD34+ cells expressing the T cell-associated molecule CD7+ in UCB (7%) compared with both PB and BM (3-4%). In general, circulating CD34+ cells, either from UCB or G-CSF-mobilized PB, display largely the same phenotypic profile and clonogenicity, being different from resident CD34+ cells in BM.
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PMID:Comparison of the phenotype and clonogenicity of normal CD34+ cells from umbilical cord blood, granulocyte colony-stimulating factor-mobilized peripheral blood, and adult human bone marrow. 753 6

Human umbilical cord blood (CB) is a rich source of hematopoietic stem cells for both research and stem cell transplantation. In clinical studies, it appears that recovery from myeloablative therapy using CB requires significantly fewer cells than a typical allogeneic marrow transplant. This suggests that CB may be enriched for early hematopoietic progenitors. The present studies were undertaken to determine the presence of CD34+ cells in CB with the phenotypic characteristics of multipotential stem cells. In 22 CB harvests, the average percentage of CD34+ cells was 1.33 +/- 0.21% (SE), a value similar to that in adult normal bone marrows (BM). However, the distribution of CD34+ cells was distinctly different from either BM or granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell harvests. CB contained a defined population of brightly staining CD34+ cells with low side scatter. These CD34 (bright) cells comprised a mean of 14.5 +/- 2.5% of the CB CD34+ cells, whereas < 1% of BM CD34+ cells has been shown to be CD34- bright. Eighty-five to ninety percent were negative for three antigens expressed at an early stage of stem cell maturation: CD38, HLA-DR and LFA-1. Fifty-five percent of these CD34 (bright) cells did not express the CD45RA isoform, an additional marker of immaturity. The antigen-bright cells also lacked lineage-specific antigens including CD33, CD56, CD19, CD10 and CD7 as well as CD71. Approximately 46% were Thy-1+, and 40% expressed c-kit receptors. These data suggest that, by phenotypic criteria, CB may be a particularly enriched source of primitive hematopoietic precursors.
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PMID:A unique population of CD34+ cells in cord blood. 754 Apr 69

We report on a patient with cyclic neutropenia who was treated by granulocyte colony-stimulating factor (G-CSF) and high-dose immunoglobulin. The serial examination revealed cyclic fluctuations in the numbers of neutrophils, monocytes, platelets in peripheral blood, and in the serum G-CSF concentration. Bone marrow examination confirmed a cyclic fluctuation of both progenitor cells (CFU-GM) and CD10-positive B cells. The therapy of G-CSF followed by high-dose immunoglobulin achieved a disappearance of neutrophil oscillations. It suggested that the combination therapy of G-CSF with high-dose immunoglobulin might be effective for cyclic neutropenia.
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PMID:Disappearance of neutrophil fluctuations in a child with cyclic neutropenia by combination therapy of granulocyte colony-stimulating factor and high-dose immunoglobulin. 754 58

Neutral endopeptidase 24.11 (NEP/CALLA/CD10), an enzyme expressed on early lymphoid progenitors, neutrophils, and various other cell types, inactivates many biologically active peptides, including the bacterial chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Inhibition of CD10/NEP on the surface of human neutrophils (PMNs) in vitro inhibits migration toward this chemotaxin, suggesting that enzymatic inactivation by NEP regulates the neutrophil response to fMLP. Because PMNs in inflammatory sites are exposed to various cytokines, we evaluated the effects of selected cytokines on CD10/NEP activity in vitro. Of five cytokines tested--interleukin-1 (IL-1), IL-6, and IL-8, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor (GM-CSF)--GM-CSF provided the most consistent increase in surface NEP activity. Low concentrations (10(-9)-10(-7) M) of GM-CSF increased NEP activity in a time- and concentration-dependent manner to more than 225% that of control (phosphate-buffered saline-treated) cells. Cytofluorometry of cells stained with a fluorescent antibody to CD10 indicated that GM-CSF increased expression of surface CD10/NEP antigen in a similar manner. The effect of GM-CSF on NEP activity was enhanced still further by simultaneous exposure to IL-1, suggesting that combinations of cytokines may direct and regulate the neutrophil response within an inflammatory site. Rapid upregulation of CD10/NEP underscores the importance of this enzyme for control of peptide mediators of inflammation.
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PMID:Up-regulation of neutral endopeptidase (CALLA) in human neutrophils by granulocyte-macrophage colony-stimulating factor. 831 51

Remission marrow from patients with BCR-ABL+ acute lymphoblastic leukemia (ALL) achieving clinical remission (CR) after induction or consolidation chemotherapy according to the German multicenter adult ALL (GMALL) protocol showed high titers of residual BCR-ABL+ cells. Therefore, we initiated a pilot study to monitor circulating BCR-ABL+ cells and to collect, purge, and autograft peripheral blood stem cells (PBSC) in these patients. After GMALL 05/93 high-risk phase II of induction chemotherapy (high-dose AraC 3 g/m2 x 8 does and mitoxantrone 10 mg/m2 x 3 doses), patients received 5-10 micrograms/kg subcutaneous recombinant human granulocyte colony-stimulating factor (rhG-CSF) daily. Mobilized CD34+ cells peaked between 20 and 26 days after starting chemotherapy at 4.8-75.6 (median 10.8) x 10(4)/mL peripheral blood (PB) (n = 5). Patients treated with additional chemotherapy cycles failed to mobilize adequate numbers of CD34+ cells. PB stem cells (PBSC) were purged using a cocktail of CD10, CD19, and AB4 monoclonal antibodies (mAbs) coupled to immunomagnetic beads (IMB). The median recoveries of total nucleated cells (TNC) and CD34+ cells after mAb/IMB purging were 84 and 81%. The peak numbers of CD34+ cells collected in a single leukapheresis were median 8.6 x 10(6)/kg pre- and 5.2 x 10(6)/kg postpurge (n = 4). The absolute prepurge CD19+ cells were as low as median 2.7 (range 1.4-19) x 10(6) per leukapheresis. Residual BCR-ABL+ cells in unpurged leukapheresis products were assessed by limiting-log10-dilution nested reverse-transcriptase polymerase chain reaction (RT-PCR) as one in 10(5) to one in 10(6) normal cells and were consistently undetectable in all purged PBSC autografts. We conclude that sufficient numbers of CD34+ cells for PBSCT can be collected after phase II but not at later stages of the GMALL 05/93 high risk protocol; PBSC grafts are 3 log less contaminated with residual BCR-ABL+ cells compared to an historical series of 13 autologous BM grafts; and purging of PBSC with mAb/IMB is feasible with minor loss of CD34+ cells and abolished BCR-ABL signals in the grafts.
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PMID:Purging of peripheral blood stem cells yields BCR-ABL-negative autografts in patients with BCR-ABL-positive acute lymphoblastic leukemia. 854 55

We report the results of a recent trial in elderly acute lymphoblastic leukemia (ALL) patients (> or = 60 years). Initial chemotherapy consisted of one 14-day course with single-dose idarubicin plus vincristine-prednisone-L-asparaginase. Idarubicin was preferred to other anthracyclines because of its shorter time to response. Sequential outpatient postremission therapy included single-dose idarubicin plus vincristine-cyclophosphamide-L-asparaginase pulses, cranial irradiation with intrathecal methotrexate-cytarabine, flexible weekly vincristine-cyclophosphamide alternating with cytarabine-teniposide, and two-year standard maintenance with mercaptopurine-methotrexate. Granulocyte colony-stimulating factor (G-CSF) was added to induction and early consolidation courses. Twenty-two patients mainly with high-risk features entered the study: median age was 64 years (60-73), 40% of cases were CD10- B-lineage and T-lineage ALL, 38% of CD10+ B-lineage ALL carried a BCR-ABL rearrangement, while 23% coexpressed myeloid antigen, 86% had L2 morphology, 50% had a blast count greater than 10 x 10(9)/1, 54% had hepato-splenomegaly and lymphadenopathy. The complete remission (CR) rate after induction therapy was 59%. A partial remission was obtained in two cases. There were four early deaths (18%) and three refractory ALL (14%). Median time to response was 21 days. With G-CSF, the median duration of absolute neutropenia was 10.5 days. Flexible postremission therapy was very well tolerated, causing no major toxicity. With a median follow-up of 2.6 years, 3 patients remain alive in first CR (23%), 2 of whom at 21.3 months and 39.6 months, respectively. Median survival of responders was 12 months compared to only 1.2 months for nonresponders (p < 0.001). This moderate-dose idarubicin-containing and G-CSF-supported regimen was associated with a high early remission rate in elderly ALL. Postremission therapy results were modest, though not appreciably different from the general experience in this patient population. Because further escalation of drug intensity appears unjustified, attempts to document and reverse drug resistance patterns and restore a dysregulated apoptosis must be considered.
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PMID:Age-adapted moderate-dose induction and flexible outpatient postremission therapy for elderly patients with acute lymphoblastic leukemia. 881 79


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