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At least 19 recordsLinked to original sources
PubMed1991

Increased lysis of patient CD10-positive leukemic cells by T cells coated with anti-CD3 Fab' antibody cross-linked to anti-CD10 Fab' antibody.

An anti-CD3 Fab' x anti-CD10 Fab' bispecific hybrid F(ab')2 antibody (Ab) was generated. This bispecific Ab had a molecular mass of 100 to 110 Kd, and the capacity to react with both CD3+ T cells and CD10+ acute lymphoblastic leukemia (ALL) cells. We studied whether cytotoxic T lymphocytes (CTLs) could lyse patient CD10+ ALL cells after addition of the bispecific Ab. As effector CTLs, interleukin-2 (IL-2)-stimulated peripheral blood mononuclear cells (PBMCs) and CTL clones were used. When IL-2-stimulated PBMCs were assayed for cytotoxicity to 61Cr-labeled CD10+ ALL cells, their activity was shown to be markedly enhanced by the addition of the bispecific Ab. Most of the CTL clones established lacked cytotoxicity for CD10+ ALL cells, but addition of the bispecific Ab induced a significant level of cytotoxicity. CTLs derived from ALL patients also showed significant cytotoxicity for autologous CD10+ ALL cells after addition of the bispecific Ab. However, this Ab did not affect the cytotoxicity of CTLs when CD10- leukemic cells were used as the targets. These findings suggest that the bispecific Ab can be used for immunotherapy in patients with CD10+ ALL.

Antigens, CD↗
PubMed1990

Characterization of the common acute lymphoblastic leukaemia antigen (CD10) as an activation molecule on mature human B cells.

Distinct expression pattern of CD10 molecules during B cell activation was analysed using in vivo and in vitro systems. By two-colour flowcytometrical analysis, CD10 was found to be expressed at a specific stage of in vivo activating B cells. The expression of CD10 during B cell activation appeared to be unique from that of other activation-related B cell antigens including L29, MA6, OKT9 and OKT10. Although the expression of CD10 was associated with that of the activation-related B cell antigens, CD10+ B cells could be separated in the distinct fractions to those expressing other activation-related B cell antigens when fractionated by cell gravity. In particular, certain CD10+ B cells were detected positive for the resting B cell antigen, L30. In vitro studies revealed that CD10+ B cells arose from CD10- B cells at an early step of B cell activation, and disappeared lately when activated by Staphylococcus aureus Cowan I. Collectively, CD10 was an antigen transiently expressed at an early phase of B cell activation process. Expression of CD10 and other antigens on Burkitt's lymphomas (15 cases) was studied next. All cases were CD10+, and 87% (13 cases) were also L30+. In addition, six of CD10+ L30+ cases were L29+. This observation suggested that Burkitt's lymphomas were phenotypically similar to the B cells at an early phase of activation, those expressing CD10 and L30, simultaneously. The present study has dissected a precise expression pattern of CD10 on mature B cell activation in vitro and in vivo, and could be implicated for the histogenesis of one of the poorly characterized B cell lymphoma, namely Burkitt's lymphoma.

Antigens, CD↗
PubMed1992

Induction of isotype switching and Ig production by CD5+ and CD10+ human fetal B cells.

In the present study the capacity of early fetal B cells to produce Ig was investigated. It is shown that B cells from fetal liver, spleen, and bone marrow (BM) can be induced to produce IgM, IgG, IgG4, and IgE, but not IgA, in response to IL-4 in the presence of anti-CD40 mAb or cloned CD4+ T cells. Even splenic B cells from a human fetus of only 12 wk of gestation produced these Ig isotypes. IFN-alpha, IFN-gamma, and transforming growth factor-beta inhibited IL-4-induced IgE production in fetal B cells, as described for mature B cells. The majority of B cells in fetal spleen expressed CD5 and CD10 and greater than 99% of B cells in fetal BM were CD10+. Highly purified CD10+, CD19+ immature B cells and CD5+, CD19+ B cells could be induced to produce Ig, including IgG4 and IgE, in similar amounts as unseparated CD19+ B cells. Virtually all CD19+ cells still expressed CD10 after 12 days of culture. However, the IgE-producing cells at the end of the culture period were found in the CD19-,CD10- cell population, suggesting differentiation of CD19+,CD10+ B cells into CD19-,CD10- plasma cells. Pre-B cells are characterized by their lack of expression of surface IgM (sIgM). Only 30 to 40% of BM B cells expressed sIgM. However, in contrast to sIgM+,CD10+,CD19+ immature B cells, sorted sIgM-,CD10+,CD19+ pre-B cells failed to differentiate into Ig-secreting cells under the present culture conditions. Addition of IL-6 to these cultures was ineffective. Taken together, these results indicate that fetal CD5+ and CD10+ B cells are mature in their capacity to be induced to Ig isotype switching in vitro as soon as they express sIgM.

Antibody Formation↗
PubMed1992

In vivo and in vitro antitumor activity of mitomycin C conjugates at 7-N position through a linker containing thiocarbamate bond with CD10 monoclonal antibody.

Through a linker containing thiocarbomate bound to the 7-N position of mitomycin C (MMC), conjugates with a monoclonal antibody to CD10 (NL-1) were prepared, and their antitumor activities were examined. All five conjugates, except one, showed in vitro cytotoxicity to two CD10+ lymphoid cell lines superior to MMC. The conjugate displaying the highest cytotoxicity was selected and further tested against three CD10+ and two CD10- lymphoid cell lines in vitro. The conjugate with NL-1 antibody demonstrated higher cytotoxic activity against CD10+ tumor cells than the control conjugate with normal immunoglobulin, while there was no significant difference, when tested against CD10- tumors. The cytotoxic activity of the NL-1 conjugate to CD10+ tumors was significantly blocked by NL-1 antibody. In vivo antitumor activity of the NL-1 conjugate was then tested against a CD10+ tumor transplanted to nude mice, and side effects were recorded. The NL-1 conjugate (4 mg/kg) showed an in vivo antitumor effect similar to MMC (2 mg/kg), which is at nearly maximal tolerable dose; the latter induced decreases in numbers of leukocytes and platelets, while the former did not, suggesting less side effect by the NL-1 conjugate. Since MMC demonstrates a broad spectrum of antitumor activity, the conjugate, as such, may be applicable for the treatment of cancer patients.

Animals↗
PubMed1991

Regeneration of CALLA (CD10+), TdT+ and double-positive cells in the bone marrow and blood after autologous bone marrow transplantation.

In this prospective study we investigated the frequency of CD10+, TdT+ and CD10+TdT+ mononuclear cells in the bone marrow (BM) and peripheral blood (PB) before and after autologous bone marrow transplantation (ABMT). 49 patients treated for acute lymphoblastic or myeloblastic leukaemia, malignant lymphoma or multiple myeloma were included. A significant increase in CD10+ cells occurred in BM in both children and adults after ABMT. In children, we also found a significant increase in CD10+ cells in PB. In individual patients remaining in remission, up to 34% CD10+ cells having a normal Ig kappa/lambda light chain ratio were recorded after ABMT. In children, the percentage of TdT+ and CD10+ TdT+ cells increased significantly in BM. In most cases the CD10/TdT-ratio was greater than 1.0, but during early regeneration after ABMT this ratio was less than 1.0 in several patients remaining in complete remission. In patients remaining in remission, CD10+TdT+ cells were detected in the blood in only 2 out of 140 samples tested, and the proportion of these cells never exceeded 0.03%. We conclude that quantitation of CD10+TdT+ cells in peripheral blood is helpful in the evaluation of complete remission in patients treated for pre-B-ALL.

Adult↗
PubMed1991

Purine metabolism enzyme pattern, cytochemical characteristics and clinicopathologic features of CD10-positive childhood T-cell leukemia.

Purine metabolism enzyme pattern, cytochemical markers and clinicopathologic features of common acute lymphoblastic leukemia antigen (cALLA; CD10)-positive, CD10-negative T acute lymphoblastic leukemia (ALL), and cALLA-positive non-T, non-B ALL (common ALL; C ALL) of children were compared. The results of immunophenotyping of blast cells in 61 children with ALL who were treated and followed during the last 7 years at the Second Pediatric Clinic in Bratislava are presented. The aim of our study was to determine the correlation of CD10 marker expression with purine enzyme activities and clinical course in ALL of children. Immunologic phenotype performed by a panel of monoclonal antibodies in indirect immunofluorescence assay revealed 3 main ALL groups: Common ALL (C ALL), T ALL and CD10+ T ALL (C + T ALL). An additional exact cytochemical marker analysis was performed in these three ALL immunologic subtypes. Two enzymes of purine metabolism, i.e. adenosine deaminase (ADA) and purine nucleosidephosphorylase (PNP) were investigated in blast cells by paper radiochromatography. Life-table analysis revealed significant prognostic differences with regard to event-free survival and overall survival in followed groups of ALL patients. Our results showed a rather high frequency of mixed (C + T) ALL phenotype. The characteristic T ALL enzyme pattern (high ADA, low PNP) was present not only in T, but also in CD10+ T ALL blast cells. The T cell marker showed to be dominant in the determination of clinical course and prognostic significance in children with ALL; children with T and CD10+ T ALL phenotype, in contrast to C ALL phenotype, experienced more frequent relapses and a shorter event-free survival.

Acid Phosphatase↗
PubMed1989

Expression of the common acute lymphoblastic leukemia antigen (CD10) in mesenchymal tumors.

The expression of the CD10 antigen, formerly designated as common acute lymphoblastic leukemia antigen and recently identified as neutral endopeptidase, was examined immunohistochemically in 26 benign and in 55 malignant mesenchymal tumors. CD10 expression was found in 4 of 4 leiomyomas, 7 of 10 leiomyosarcomas, 1 of 6 rhabdomyosarcomas, 2 of 2 Triton tumors, 1 of 2 aggressive fibromatoses, 1 of 3 fibrosarcomas, 1 of 4 synovial sarcomas, 1 of 1 giant cell tumors of tendon sheath, 4 of 4 malignant fibrous histiocytomas, 3 of 3 Ewing's sarcomas, and 2 of 3 osteosarcomas. Furthermore, CD10 was expressed consistently in the myoepithelial compartment of 12 fibroadenomas and, in 7 of these cases, in a minor stromal cell population, probably of (myo-) fibroblastic origin. Tumors of adipose tissue (4 lipomas, 5 liposarcomas), tumors of autonomic ganglia (2 ganglioneuromas, 1 ganglioneuroblastoma, 2 neuroblastomas), tumors of peripheral nerves with purely schwannian differentiation (7 malignant schwannomas), and tumors of disputed origin were consistently CD10-negative, however, as were single cases of fibroma and chondrosarcoma. These findings indicate that the expression of CD10 is a frequent but not obligatory feature in some mesenchymal tumors. Therefore CD10 is of value in the differential diagnosis of mesenchymal tumors.

Antibodies, Monoclonal↗
PubMed1992

CD10 antigen density in childhood common acute lymphoblastic leukaemia: comparisons of race and sex.

During the 25 month period from July 1989 until August 1991, 58 children with FAB defined acute lymphoblastic leukaemia (ALL) were referred for immunophenotypic analysis. Of these, 42 children with a common/pre-B phenotype (CD19/CD10-positive) were studied specifically to assess CD10 antigen density. A pattern of segregation was found between males and females and between black and white children. Black males, who are the worst prognostic group, had the lowest CD10 density, while white females, known to constitute the best prognostic group, had significantly higher CD10 antigen density than the other groups. Black females and white males occupied intermediate positions with respect to CD10 antigen density. A two way analysis of variance showed that although sex had contributed significantly to this variation (p = 0.0038), the contribution of race was marginal (p = 0.0530). It is hypothesized that low CD10 antigen density patterns in males and in Blacks could be causally related to poor prognosis.

Black People↗
PubMed1992

Differential kinetics of engraftment and induction of CD10 on human pre-B leukemia cell lines in immune deficient scid mice.

The sensitivity of the scid mouse model was assessed by comparing the growth of two pre-B acute lymphoblastic leukemia (ALL) cell lines, A1 and G2, established from patients at relapse. When cell numbers varying from 10(4) to 10(7) were injected intravenously into scid mice, advanced growth and dissemination of leukemia was observed at 10-12 weeks with the G2 cells. Bone marrow, spleen and thymus contained high levels of human leukemic cells and infiltration into lung, kidney, liver, and brain was observed. Two of three mice grafted with only 100 cells showed high levels of infiltration at 15 weeks, suggesting that 100 G2 cells was near the limiting cell number that could produce disseminated leukemia. With the A1 line, a minimum of 10(5) cells was needed to obtain dissemination to liver, lung, brain, and kidney; a low level of spleen infiltration occurred and thymus invasion was not observed. In vitro, both lines showed a density dependent growth in clonogenic assays but the cloning efficiency of the A1 line was 10-fold higher than for G2 cells. These results indicate that G2 and A1 lines have a dissimilar aggressiveness in vivo which does not correlate with clonogenic assay in vitro. Neither G2 nor A1 lines, growing in vitro, expressed CD10/CALLA on their surface, despite low levels of antigen on the freshly obtained relapse samples. Although A1 cells remained CD10-negative in the scid mice, G2 cells showed detectable levels of CD10, particularly on those cells found in the thymus. Several subclones of the G2 line were derived from isolated colonies in vitro; they were found to be CD10- in vitro, but to become CD10+ when proliferating into scid mouse thymus, suggesting the induction of CD10 by the murine microenvironment.

Animals↗
PubMedDate not supplied

Infusion of anti-CD10 monoclonal antibody (J5) following ablative chemotherapy in a patient with refractory pre-B acute lymphoblastic leukemia.

The case of a 9-year old girl with end-stage refractory pre-B CD10/CALLA positive acute lymphoblastic leukaemia is described. The patient was treated with high doses of cytarabine followed by intravenous anti-CD10 monoclonal antibody (J5) in an effort to prevent the recovery of the leukemic CD10 positive clone following the bone marrow hypoplasia resulting from the chemotherapy. The number of CD10 positive cells dissapeared both in the peripheral blood as well as in the bone marrow, but when granulocytic recovery ensued, the patient died from respiratory infection. No evidence of antigenic modulation of the CD10 antigen was observed in the blast cells.

Antibodies, Monoclonal↗
PubMed1990

Modulation of CALLA (CD10) antigen on cultured ALL (REH) cells: effect of various modulators.

Phorbol ester (TPA)-induced down-regulation of the common ALL (CALLA) antigen was studied by continuous flow immunocytometry with the aid of several CD10 monoclonal antibodies, including a new CD10 monoclonal antibody (DGH-10-1-A9), shown to be of IgG1 isotype, recognizing a 100 kDa cell surface protein and effectively inhibited by a series of reference CD10 monoclonal antibodies. The TPA-induced down-regulation of CALLA on REH cells was demonstrated with the aid of the following CD10 monoclonal antibodies: J-5, VIL-A1 and DGH-10-1-A9. No major modulations in cell surface expression of CALLA on REH cells were observed after induction with 1,25-(OH)2 vitamin D3, retinoic acid, recombinant interferon (IFN) alpha 2a and recombinant interleukin 2.

Antibodies, Monoclonal↗
PubMed1992

The increase of low density subpopulations and CD10 (CALLA) negative neutrophils in severely infected patients.

We investigated the changes in polymorphonuclear leukocyte (PMN) subpopulations that accompany severe bacterial infection and examined their usefulness as a parameter for assessing the severity of infection. The Percoll density gradient was used to fractionate neutrophils into subpopulations of high density (1.09-1.10), intermediate density (1.08-1.09), and low density (1.07-1.08) with the majority of neutrophils from normal volunteers being of high density. By contrast, neutrophils from infected patients were of intermediate or low density, while those from severely infected patients showed a high percentage of the low density fraction with functional changes in lower chemotactic and beta-gulcuronidase activity. When each density subpopulation in the normal blood neutrophils was tested, low density PMNs had the lowest chemotaxis and minimal beta-glucuronidase activity. These results indicate that the increase in low density PMNs in patients with severe infection clearly reflects the functional impairment of PMNs. Flow cytometric analysis demonstrated that the neutrophils from severely infected patients had an decrease in CD10 expression. The percentage of CD10 positive PMNs correlated well with the severity of infection and with the clinical course of the patients. Thus, we conclude that PMN-density and CD10 expression change during severe bacterial infection, and that the measurement of PMN-subpopulations may be used to complement the clinical assessment of the severity of infections.

Bacterial Infections↗
PubMed1987

In vitro depletion of clonogenic cells in adult acute lymphoblastic leukemia with a CD10 (anti-cALLA) monoclonal antibody.

A semi-solid medium colony assay was used in common acute lymphoblastic leukemia (cALL) to test growth inhibition of leukemic progenitors (CFU-L) after exposure to monoclonal antibodies (MoAbs) directed against CD10 and CD9 antigens. Peripheral or bone marrow cells from 15 patients were plated after exposure to various concentrations of ALB2, a CD10 cytotoxic MoAb, followed by complement lysis. CFU-L inhibition was complete (no residual colony) in 5 cases (33%), marked (greater than or equal to 95%) in 4 cases (27%), but only moderate (64% +/- 28) in 6 cases (40%). This inhibition was not related to the percentage of cALLA positive cells before exposure to MoAb. In addition, cells of 5 patients were exposed to BA1 (CD24) + complement. In these cases, the proportion of CFU-L inhibition was equal to or higher than with ALB2. In 3 cases, cells were exposed to an association of ALB2 and SB4 (CD19) MoAbs followed by complement lysis, with a marked inhibition (greater than or equal to 99%) in 2/3 cases. These observations give supplementary support to the use of several MoAbs directed against various antigens present at early stages of B differentiation.

Adolescent↗
PubMed1990

Leukemia-specific serum from a child showing an immunofluorescent pattern distinct from J-5 monoclonal antibody directed for CD10 (common ALL antigen).

Leukemia-specific human antibody was detected in a child with acute lymphoblastic leukemia (ALL) treated with chemoimmunotherapy. Chemoimmunotherapy consists of standard chemotherapy and subcutaneous injections of irradiated ALL cells with a biological response modifier. This ALL-specific serum reacted in 60 out of 67 (89.5%) children with ALL and was not reactive with normal cells. Furthermore, this ALL-specific serum showed a different immunofluorescent pattern on dual staining as compared with J-5 monoclonal antibody directed for common ALL antigen (CALLA; CD10). J-5 did not block the reactivity of ALL-specific serum, and vice versa, when CD10-positive ALL cell lines were used as targets. These findings suggest the possibility that there exists an ALL-specific antigen(s) which is different from CALLA and that this antigen(s) elicits a tumor-specific antibody response.

Antibodies, Monoclonal↗
PubMed1992

Characterization of murine CD10, an endopeptidase expressed on bone marrow adherent cells.

The CD10/neutral endopeptidase (NEP) gene was identified in murine genomic DNA using a human CD10 cDNA probe. It is transcribed most abundantly in kidneys resulting in RNA transcripts of 3.4, 6.0, and 6.2 kb. The activity of the murine CD10/NEP shows identical kinetic parameters, Km and Ki, to those observed for this enzyme in other species. Two mAbs raised against rabbit NEP detect a 100 kDa protein by Western blot analysis; the antigen immunoprecipitated from extracts of lung shows specific NEP activity. CD10/NEP, as analyzed by Western blot and enzymatic activity, is expressed at high levels in kidney and lung, and at lower levels in liver, brain, thymus, spleen, and bone marrow. Analysis of bone marrow subpopulations indicate that the majority of CD10/NEP is associated with cells adherent to plastic and with subpopulations that do not express the surface markers AA4.1, B220, Mac-1, and Gr-1. These results suggest that CD10 is primarily associated with the stromal elements in murine bone marrow. A bone marrow stromal line, BMS 2.2, also expresses high levels of CD10/NEP. This peptidase activity on the surface of stromal cells may influence lymphopoiesis or other hematopoietic processes through the hydrolysis of regulatory peptides in the microenvironment.

Animals↗
PubMed1992

Human endometrial stromal cells and decidual cells express cluster of differentiation (CD) 13 antigen/aminopeptidase N and CD10 antigen/neutral endopeptidase.

With specific monoclonal antibodies, we found that human endometrial stromal cells and decidual cells express two function-related surface antigens. Indirect immunofluorescence staining revealed that both endometrial stromal cells and decidual cells during the first trimester of pregnancy expressed cluster of differentiation (CD) 13 antigen and CD10 antigen, which are identical to aminopeptidase N and neutral endopeptidase, respectively. By flow cytometric analysis, CD13 antigen was detected on 82-93% of the examined cells, and CD10 antigen was detected on 75-93% of the examined cells in endometrial stromal cell-enriched preparations. Furthermore, peptidase activity was detected in these cell preparations by an assay based on the hydrolysis of alanine-p-nitroanilide into p-nitroaniline and alanine.

Adult↗
PubMed1989

Investigation of the CD10 (cALLA) negative acute lymphoblastic leukaemia: further description of a group with a poor prognosis. French Groupe d'Etude Immunologique des Leucémies.

The absence of CD10 (cALLA) in non-T non-B acute lymphoblastic leukaemia (ALL) is usually considered to be of adverse prognostic significance. From a large multicentre series of phenotyped ALL, we have identified a group of 23 non-T non-B ALL where blast cells were CD10 negative and CD19 positive. Class II antigens were present in 80% and C19 in 70%. Eight patients had successful karyotype analysis at diagnosis, and an additional patient at first relapse. Seven of these karyotypes showed a (4;11) (q21;q23) translocation. Most of the patients (70%) were young females, and they often presented with organomegaly. Six patients were less than 1 year old. The white cell count was over 100 x 10(9)/l in 48% of the cases. The FAB type was L2 in 56% of the patients. The most striking features were the poor response to therapy and survival. Six patients never attained complete remission and nine patients relapsed, most of them during the first year after diagnosis. Allogeneic bone marrow transplantation was performed in three children, of whom two are still alive 2 years after diagnosis. This study emphasizes the prognostic value of immuno-phenotypic and karyotypic investigations of ALL.

Adolescent↗
PubMed1991

Rapid increases in the membrane expression of neutral endopeptidase (CD10), aminopeptidase N (CD13), tyrosine phosphatase (CD45), and Fc gamma-RIII (CD16) upon stimulation of human peripheral leukocytes with human C5a.

Rapid increases in the membrane expression of C3 receptors on granulocytes and monocytes in response to the anaphylatoxin C5a have previously been described. In this study we demonstrate increases in the membrane expression of neutral endopeptidase (NEP, CD10, CALLA), aminopeptidase N (APN, CD13), tyrosine phosphatase (CD45/CD45Ro) and the Fc R Fc gamma-RIII (CD16) on granulocytes within minutes of treatment with human C5a. Monocytes responded to C5a with increases in CD13 and CD45/CD45Ro. These membrane modulations could be prevented by preincubating the C5a preparations with anti-C5a mAb C17/5 but not by pretreating the cells with cycloheximide. Increases of CD10, CD13, and CD11b but not CD11a (LFA-1) were also observed in leukocytes from patients undergoing hemodialysis with cuprophan membranes. The increase of CD16 on granulocytes was dependent on the presence of plasma during in vitro activation with C5a indicating that plasma contains inhibitors which prevent the previously described loss of Fc gamma-RIII upon stimulation of the cells.

Aminopeptidases↗