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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↗

PubMed1997

CD10 plays a specific role in early thymic development.

Development of T lymphocyte is a complex process that depends on both thymocytestromal cell interactions and the production of soluble factors such as cytokines, peptides, and hormones. In many tissues, the concentration of active biological peptides is regulated locally by a specialized family of enzymes: the ectopeptidases. We show here that treatment of fetal thymic organ cultures (FTOC) with the specific CD10 (endopeptidase 24.11) inhibitors SCH 32615: (N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine), RB25: (N-(3-[(hydroaxyamino)carbonyl]-2-benzylidene-1-oxopropyl]-N-glyci ne), and thymopentin (TP5) results in the inhibition of thymocyte differentiation. Each agent induces a significant decrease in the number of double positive (CD4+CD8+) cells in favor of the TN (TcR alpha beta-CD4-CD8-) population. RB25 also blocks T lymphocyte differentiation in FTOC when preinjected into pregnant mice. Finally, RB25 and TP5 were also shown to reduce the number of CD44+CD25- and CD44-CD25- thymocytes both in vitro and after preinjection in vivo in day 2 FTOC. Thus, agents that affect endopeptidase 24.11 activity impair T cell development both in vitro and in vivo. Our results show that the CD10 molecule plays a specific role in promoting early T cell development.

Animals↗

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↗

PubMed1995

An infantile case of cytomegalovirus induced idiopathic thrombocytopenic purpura with predominant proliferation of CD10 positive lymphoblast in bone marrow.

An infant with cytomegalovirus infection (CMV) developed idiopathic thrombocytopenic purpura (ITP) at 4 months of age. A bone marrow (BM) aspiration showed a remarkable increase of immature megakaryocytes and prominent proliferation of lymphoblasts. Flow cytometric analysis of the bone marrow cells showed that the predominant cells in the lymphocyte cluster were of B-lineage (CD19) with CD10 (common acute lymphoblastic leukemia antigen) positive. Virus study showed a higher titer of CMV antibody. Cytomegalovirus DNA was detected by the polymerase chain reaction (PCR) method in urine, peripheral cells and marrow cells. Low-grade fever, diarrhea and petechiae were accompanied by mild liver dysfunction. Complete remission was made with intravenous high-dose immunoglobulin (IVIg) without progression to overt acute leukemia. The percentage of CD10+/CD19+ lymphocytes in bone marrow also diminished. We postulated that the proliferation of immature lymphocytes and megakaryocytes in bone marrow was caused by maturation arrest that might result from CMV infection.

Antigens, CD↗

PubMed2006

The role of immunohistochemistry for smooth-muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast.

BACKGROUND: Histological differentiation of mammary papillary lesions can be difficult. The evaluation of myoepithelial cells can be helpful, with benign papilloma showing a continuous myoepithelial cell layer, which becomes attenuated or absent in malignant papillary lesions. METHODS: A large series of 100 papillomas (28 papillomas with florid epithelial hyperplasia) and 68 papillary carcinomas (9 invasive, 44 in situ, and 15 ductal carcinomas in situ (DCIS) involving papillomas) of the breast were stained for myoepithelial cells by immunohistochemistry using antibodies to smooth-muscle actin (SMA), p63, CD10 and cytokeratin (CK) 14. RESULTS: In the papillomas, using these four antibodies, myoepithelial cells were positive in 88%, 99%, 91% and 95% of cases, respectively, with SMA showing marked stromal component cell staining and CD10 showing epithelial and stromal staining. CK14 also showed epithelial staining in 71% of papillomas and 96% of papillomas with florid epithelial hyperplasia. In the papillary carcinomas, 36 (53%) cases showed staining of myoepithelial cells that were scattered, discontinuous and diminished in number and the remaining 32 (47%) cases did not show myoepithelial cells. Invasive papillary carcinoma has the lowest proportion (33%) with myoepithelial cells, and DCIS involving papillomas had the highest proportion (87%). CONCLUSIONS: p63 had the highest sensitivity and did not cross-react with stromal cells and only rarely with epithelial cells. CK14 has the added ability to distinguish between florid epithelial hyperplasia involving papilloma and DCIS involving papillomas. CK14 and p63 may be used as an adjunct in assessing difficult papillary lesions of the breast.

Actins↗

PubMed1999

CD10 positive thyroid marginal zone non-Hodgkin lymphoma.

A 72 year old woman presented with swelling of the right lobe of her thyroid gland. Fine needle aspiration and flow cytometry showed a clonal population of B cells expressing CD10 and a diagnosis of follicle centre cell lymphoma was made. Subsequent excision of the thyroid showed the typical histological features of a marginal zone non-Hodgkin lymphoma. Polymerase chain reaction showed no evidence of t (14;18). Immunohistochemistry confirmed CD10 positivity and LN1 (CDw75) expression. This is only the second report of aberrant expression of CD 10 by a marginal zone lymphoma.

Aged↗

PubMed2004

Expression of bcl-6 and CD10 protein is associated with longer overall survival and time to treatment failure in follicular lymphoma.

Follicular lymphomas (FLs) are a heterogeneous group of tumors, but prognostic factors are evaluated insufficiently in this common hematologic neoplasm. While bcl-6 and CD10 are expressed characteristically in FLs, their significance for biologic behavior of FL has not been studied previously. Samples from 73 patients with FL and clinical follow-up from 7 to 231 months were evaluated by immunohistochemical analysis. Patients with high levels of bcl-6 expression had favorable overall survival (OS) (P = .003), disease-specific survival (DSS) (P = .033), and time to treatment failure (P = .003) compared with patients with low levels of bcl-6 expression. Multivariate analysis showed that the results for OS, DSS, and time to treatment failure were independent of the international prognostic index. Patients with CD10+ FLs also had longer OS (P = .001), DSS (P = .007), and time to treatment failure (P = .004), and grade 1 FL was associated with better OS (P = .01) and a statistical trend for longer DSS (P = .05) and time to treatment failure (P = .05), but these results were not independent of bcl-6 expression or the international prognostic index in multivariate analysis.

Adolescent↗

PubMed2006

The usefulness of CD71 expression by flow cytometry for differentiating indolent from aggressive CD10+ B-cell lymphomas.

We studied 34 low- and 30 high-grade CD10+ B-cell lymphomas. Forward light scatter (FSC) and CD71 fluorescence intensity (CD71i) of tumor cells were measured and normalized by corresponding values for resting T cells. Significant differences in CD71i values between low- and high-grade lymphomas were observed by the Mann-Whitney U test (P < .001) and receiver operating characteristic (ROC) curve analysis (P < .001). FSC was not significantly different between low- and high-grade lymphomas; the area under the ROC curve was less than that for CD71i. Neither FSC nor CD71i significantly differentiated follicular lymphoma (FL) grades. A comparison of all FLs (grades 1-3) and non-FL high-grade lymphomas (Burkitt lymphoma [BL] and large B-cell lymphoma [LBCL]) showed significant differences in CD71i (P < .001) and FSC (P = .021). Differences were significant in CD71i and FSC between FL and LBCL (P < .001) but not between FL and BL. CD71i is more potent than FSC for distinguishing CD10+ low- from high-grade lymphomas and FL from non-FL high-grade lymphomas. Sensitivity and specificity are limited owing to inability to identify FL3. In ROC analysis, a high value for CD71i can identify BL and LBCL with a high degree of certainty.

Antigens, CD↗

PubMed1994

Antibody-induced modulation and intracellular transport of CD10 and CD19 antigens in human malignant B cells.

Antibody-induced antigenic modulation (AIAM) is a complex biological phenomenon closely resembling other receptor-ligand interactions. Following exposure to specific antibodies, surface antigens are usually rapidly redistributed on the cell surface and internalized. A subsequent intracellular processing results in dissociation of the antigen-antibody complexes, degradation, exocytosis and recycling. AIAM plays an important role in MoAb-targeted therapy of hematopoietic malignancies contributing to escape of tumor cells from immunodestruction. On the other hand, internalization of MoAbs used as carriers of toxins and drugs is a prerequisite of therapeutic efficacy. Even though MoAbs directed against CD10 and CD19 have been used in immunotherapy of B cell malignancies, some aspects regarding AIAM of these Ags are not yet fully understood. Both Ags are modulated by specific MoAbs and internalized through the same pathway, however, the kinetics of AIAM vary from one Ag to another and from one cell type to another. Recent studies with malignant B-cell lines show that, under certain experimental conditions, the extent and rate of surface clearing, uptake and intracellular transport are considerably higher in the case of CD19 than in CD10 and higher in less mature cells compared with more mature cells. These observations may be useful in the selection of MoAbs for immunotherapy, although they need to be confirmed with fresh malignant B cells.

Antibodies, Monoclonal↗

PubMed1998

PreB1 (CD10-) acute lymphoblastic leukemia: immunophenotypic and genomic characteristics, clinical features and outcome in 38 adults and 26 children. The Groupe dEtude Immunologique des Leucémies.

The less differentiated stage (CD10-) of B-lineage acute lymphoblastic leukaemia (ALL) described as preB1-ALL in the GEIL nomenclature, accounts for less than 10% of ALL. It is classically considered to be associated with translocation (4;11)(q21;q23), and to have a poor prognosis. We report an extensive immunophenotypic, genomic and clinical study of a series of 64 preB-1 ALL patients, representing 6.3% of a cohort of consecutive ALLs. The engagement of preB1-ALL cells in the B-lineage was confirmed by their B-lineage score, equal to or higher than 2. In addition, more than 90% of the cases tested showed rearranged IGH genes. Translocation (4;11) was the most frequent karyotypic anomaly seen, but only accounted for 24% of the preB1-ALL cases tested. Expression of the myeloid associated antigen CD15 was also found with high incidence in this subset. Clinical and biological features at presentation showed more significant differences between preB1- and T-ALL than between preB1- and preB2-ALL (CD10+). However, outcome characteristics of the 22 children with preB1-ALL confirmed the worse prognosis of this entity.

Adolescent↗

PubMed2003

The number of CD10-positive glomerular epithelial cells reflects renal prognosis in IgA nephropathy patients.

BACKGROUND: The glomerular epithelial cells play an important role in glomerular filtration of the kidney. The disruption of these cells contributes to the development of glomerulosclerosis. The present study was performed to elucidate whether loss of the glomerular epithelial cells is associated with renal injury in patients with IgA nephropathy. PATIENTS AND METHODS: Thirty renal biopsy specimens from IgA nephropathy, 12 from minor glomerular abnormalities and 5 from normal controls were observed. The specimens from IgA nephropathy were divided into 2 groups: Group IgA-1, including 11 patients who had received a follow-up renal biopsy because of deterioration of renal function, and Group IgA-2, consisting of the remaining 19 patients without follow-up biopsy. Immunohistochemistry was performed using a monoclonal antibody against CD10 antigen that appears on mature epithelial cells of glomeruli. RESULTS: The average number of CD10-positive glomerular epithelial cells (GECs) was significantly lower in IgA nephropathy than in either minor glomerular abnormalities or the normal controls. In IgA nephropathy, there were significant correlations of the GECs with renal functions. The GECs were reduced along with the progression of histopathological damage. In group IgA-1, the GECs were significantly reduced at the second biopsy compared with the first biopsy, and significantly fewer in group IgA-1 than in group IgA-2 at the first biopsy. The GECs showed a significant correlation with renal prognosis during the follow-up period. CONCLUSIONS: The reduction of GECs was associated with renal dysfunction, histopathological damage and renal prognosis. The GECs may be a useful predictor of renal prognosis in IgA nephropathy.

Adult↗

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↗

PubMed1991

CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide-induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation.

The common acute lymphoblastic leukemia antigen (CALLA, CD10), which is expressed on early lymphoid progenitors and neutrophils, is the zinc metalloprotease, neutral endopeptidase 24.11 (NEP, "enkephalinase"). The CD10 cell surface enzyme is known to hydrolyze a variety of biologically active peptides including met-enkephalin, formyl-met-leu-phe (f-MLP), and substance P. These three CD10/NEP substrates induce the migration and aggregation of neutrophils, suggesting that each of the peptides can function as a mediator of neutrophil inflammatory responses. Recently, inhibition of CD10/NEP was found to reduce the concentration of metenkephalin needed to activate human and invertebrate granulocytes by several orders of magnitude. Herein we show that f-MLP and substance P induce rapid changes in neutrophil morphology, migration, and adhesion molecule expression, including upregulation of Mo1 (CD11b/CD18) and shedding of LAM-1 (also known as LECAM-1, Leu8, or TQ-1, the human homologue of murine gp100MEL14). Importantly, these coordinated changes are potentiated by inhibition of cell surface CD10/NEP enzymatic activity. Neutrophil cell surface CD10/NEP enzymatic activity is also shown to be regulated by the activation state of the cell during the time period in which the enzyme has its most pronounced effects. These results suggest that in neutrophils, CD10/NEP functions to control responsiveness to multiple inflammatory peptides.

Antigens, Differentiation↗

PubMed1995

Distribution of carboxypeptidase M on lymphoid and myeloid cells parallels the other zinc-dependent proteases CD10 and CD13.

Monoclonal antibody (MoAb) M27 was generated after immunization of mice with the human B-lineage acute lymphoblastic leukemia cell line Pre-ALP. Under reducing conditions, MoAb M27 precipitated a 60-kD surface-membrane molecule from Pre-ALP cells. Expression cloning of Pre-ALP cDNA showed that M27 recognizes carboxypeptidase M (CPM), a cell-surface, zinc-dependent protease known to cleave off basic C-terminal amino acids from peptide hormones. Using M27 antibody, CPM was detected only at discrete B lymphocyte developmental stages, namely on committed precursors and on germinal center cells. CPM was also expressed on mature T cells, mainly after activation. These results provide the first description of a carboxy-peptidase on lymphoid cells. In addition, CPM was found on granulocytes and monocytes, but not on their progenitors. Strikingly, CPM was present only on CD38+ cells, irrespective of lineage affiliation. Of interest, CPM displayed a largely overlapping distribution with the CD10 and CD13 peptidases, with which it shares common substrates (enkephalins, bradykinin). Collectively, the present data show a previously unrecognized distribution pattern of CPM on lymphoid and myeloid cells and suggest that CPM may cooperate with CD10 and CD13 to regulate biologic activity of peptide hormones on leukocytes.

ADP-ribosyl Cyclase↗

PubMed1998

Expression of CD10, CD19 and CD34 markers in bone marrow samples of children with precursor B-cell acute lymphoblastic leukemia in clinical and hematological remission.

Long-term follow-up of the rate of CD10, CD19 and CD34 antigens expression compared with the percentage of lymphocytes and blastic cells in 196 bone marrow specimens of 91 children with early B-cell acute lymphoblastic leukemia has been performed. It was shown that during a five year period there were no significant differences concerning the percentage of CD markers and the percentage of lymphocytes and blastic cells except those in the 4th year of clinical and immunological follow-up--when increase of lymphocytes and CD19 marker percentage have been observed. Consensus, i.e. more than 20% CD markers positivity associated with more than 5% blasts (positive consensus) or less than 20% CD markers positivity combined with less than 5% blasts (negative consensus) was ascertained in 92.8% of cases. Disagreement, i.e. the rate of CD markers over 20% combined with less than 5% blasts was found in 14 (7.2%) patients. This finding present in the initial phase of the disease could be considered as a sign of not complete remission, in contrast to the finding in children who completed chemotherapy and were in long-term hematological remission, in which the increase of CD markers could be considered as a sign of increased regeneration activity of bone marrow after chemotherapy induced medullary aplasia. Anyway, the increase of CD10, CD19 and CD34 antigens in bone marrow samples over 20% should be evaluated with caution. In these cases, mainly in children with long-term hematologic remission the examination should be repeatedly performed and/or more sensitive methods for detection of minimal residual disease should be applied. In control group of 20 children without leukemia the rate of CD markers in the bone marrow was always under 20%.

Antigens, CD19↗

PubMed2005

DOR-1, A novel CD10+ stromal cell line derived from progressive Langerhans cell histiocytosis of bone.

BACKGROUND: Langerhans cell histiocytosis (LCH) is granulomatous proliferative disorder characterized by the presence of activated Langerhans cells admixed with macrophages, lymphocytes, and eosinophils. In an effort to obtain an LCH ex vivo model, we succeeded in establishing the DOR-1 cell line from an LCH lesion of bone in a 3-year-old girl. PROCEDURE: The DOR-1 cell line was established from a CD1a immunoreactive LCH lesion of bone maintained in long-term cell culture. The phenotypic characteristics were assessed by immuno-cytochemistry and fluorescence activated cell sorter (FACS) analysis. Cytogenetic analysis was performed by RHG-banding that was supplemented by fluorescence in situ hybridization (FISH). RESULTS: The DOR-1 cells grew in vitro as a poorly differentiated mesenchymal-like cells with a doubling time between 72 and 96 hr. The cells exhibited pleomorphism and consistent immuno-reactivity for CD10 (50%), CD13 (55%), CD68 (65%), and CD117 (70%) while CD1a, Langerin and HLA-DR were not detected. By RHG-banding, several aberrant chromosomes were detected including the t (9; 17) (p23; p13) translocation and a pair of long dicentric marker chromosomes indicating clonal abnormality. Functionally, exposure to 33 nM 12-O-tetradecanoyl phorbol mirystate-13-acetate (TPA) induced DOR-1 cell differentiation with appearance of cytoplasmic extensions. CONCLUSIONS: The DOR-1 cell line exhibits distinct immuno-cytochemical features and carries the t (9; 17) (p23; p13) translocation suggesting involvement of stromal-like cell lineage in LCH initiation and progression.

Animals↗

PubMed2005

CD10- and CD34-positive periglandular stromal cells in pulmonary benign metastasizing leiomyoma with metaplastic adenomyomatous glands: an ultrastructural and immunohistochemical study.

Two Japanese females, 36 years and 52 years old, with episodes of uterine leiomyoma, were operated on for pulmonary benign metastasizing leiomyomas (PBMLs) in their peripheral lung. Conventional light microscopic, ultrastructural, and immunohistochemical studies revealed that the PBMLs possessed an adenomyomatous histology, consisting of metaplastic glandular structures and stromal or smooth-muscle cell proliferation. In the tumorous nodules of the PBMLs, epithelial cells with the characteristics of lung epithelial cells of type-II pneumocytes were observed, together with ciliated and non-ciliated bronchiolar epithelial cells in the entrapped and metaplastic glands. The present study pointed out the unique periglandular stromal cells of fibroblastic cells, which were lacking the immunohistochemically conventional characteristics of normal lung smooth muscle cell but showed unique characteristics-ultrastructurally: fibroblastic lacking well-developed myofilaments with dense patches and well-developed external lamina; but immunohistochemically: CD10+, CD34+, alpha-smooth-muscle actin+, desmin-, estrogen receptor+, and progesterone receptor+. It was speculated that glandular metaplasia from entrapped respiratory epithelia cells might be introduced by the possible inductive interactions of periglandular mesenchymal stromal cells. Putative microenvironmental inductive roles were postulated for the periglandular stromal fibroblasts to induce a metaplastic change toward the glands from pre-existing lung epithelial cells revealing adenomyomatous features.

Adult↗