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)

Primary bone marrow lymphomata are infrequent; most of them are of B-cell origin, and those of a T-cell lineage produce mainly both hypercalcemia and osteolytic lesions apparently due to abnormal production of osteoclast-activating factor. We report a 15-year old patient with a primary bone marrow lymphoma: 85% of his infiltrating malignant lymphocytes displayed cytoplasmic mu-chains compatible with a pre-B phenotype. The cells failed to display the CALLA/CD 10 antigen. Serum calcium was 7.5 mEq/L (range 4-5 mEq/L); the bone biopsy of an osteolytic lesion disclosed a large-cell, diffuse non-Hodgkin's lymphoma. No malignant cells were found in the peripheral blood and there were no enlarged lymph nodes. The patient was treated with 6 courses of chemotherapy: hydroxyldaunorubicin, vincristine and prednisone (HOP). Complete remission was achieved and the patient was placed on continuation chemotherapy with daily six-mercaptopurine and weekly methotrexate, together with HOP pulses every three months. The hypercalcemia disappeared together with the fever and the bone pain: the patient has been followed 6 months. Data on this case are discussed together with those previously published in regard to the low prevalence of bone lesions in primary B-cell lymphomas of the bone marrow, and to the similarity of this B-cell malignancy to others that produce both hypercalcemia and bone lesions, i.e. multiple myeloma.
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PMID:[Hypercalcemia and osteolytic lesions associated with pre-B-cell primary lymphoma of the bone marrow. A case report]. 227 Mar 71

We report here 16 autologous bone marrow transplantations (ABMT) for poor prognosis B or pre-B malignancies (16 acute lymphoblastic leukemias (ALL), three Burkitt lymphomas, one multiple myeloma) in 11 adults and five children where in vitro purging was accomplished by means of floating immunobeads. This method was developed to avoid non-specific killing by complement or toxin or batch-to-batch variability and provides a 3 log reduction of tumor in a model of B lymphoid malignancies. Low density bone marrow mononuclear cells were incubated for 30 min at 4 degrees C with anti CD10 (ALB2 Immunotech) and/or anti CD19 (Bg4) monoclonal antibodies (MoAb) and then mixed with low density polypropylene beads precoated with a rat antimouse MoAb. After 1 h at 4 degrees C the beads with target cells were decanted; the depleted marrow was collected through a microfilter and cryoperserved. After immunodepletion the recovery of nucleated cells was 75% with a median of 0.75 x 10(8) cells/kg (range 0.3-3.6) and the recovery of hematopoietic progenitors was 83% with a median of 2.9 x 10(4) CFU-GM/kg. The conditioning regimen consisted of busulfan 16 mg/kg and melphalan 140 mg/m2 for three patients, fractionated total body irradiation (TBI) following melphalan 140 mg/m2 for nine patients, TBI and cyclophosphamide 120 mg/m2 for two patients and TBI associated with melphalan and cyclophosphamide for two patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autologous bone marrow transplantation for B cell malignancies after in vitro purging with floating immunobeads. 229 92

The activity of the membrane-bound neutral endopeptidase 24.11 was low in the normal liver (21 +/- 3 pmol/h/mg protein, mean +/- SE) but it increased 56-fold in rapidly-growing rat hepatoma 3924A. The identity of the enzyme in the tumor was established by immunoprecipitation and by using a specific inhibitor of neutral endopeptidase. The endopeptidase concentration in the differentiating and regenerating liver was lower than in normal tissue, 39 and 8% of the corresponding control. The activity of a plasma membrane marker enzyme carboxypeptidase M in the normal liver was 1.0 +/- 0.2 nmol/h/mg protein, it increased about 2-fold in the rapidly-growing hepatoma and in the differentiating liver, but was unchanged in regenerating liver. The function of the strikingly increased neutral endopeptidase activity in the rapidly growing hepatoma may relate to activation of autocrine or exocellular growth factors or to inactivation of cell proliferation-inhibitory factors. Such a biochemical change should confer selective advantages to the cancer cells.
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PMID:High concentration of neutral endopeptidase (enkephalinase E.C. 3.4.24.11) in a malignant tumor: rat hepatoma 3924A. 235 Mar 55

Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood in the West, characteristically showing a peak incidence in children aged between two and five years, and being predominantly of the common ALL (cALL) phenotype. In this article, we examine the hypotheses that ALL is relatively less common among childhood malignancies in Saudi Arabia; that the cALL phenotype is uncommon; that T cell ALL (TALL) is relatively more common. We report that of 163 children with ALL seen at the King Faisal Specialist Hospital and Research Centre, we find that their median age was 5.0 years with a modal value of 3 years, with a range of 4 months to 14 years; that there were 93 cALL patients who were predominantly young (median age 5.0 years). There were 20 (12.3%) patients with TALL, whose median age was 8.5 years, 35 (21.5%) patients who were null cell ALL and whose median age was 6.0 years, 14 (8.6%) patients with B cell ALL whose median age was 9.0 years, and 3 (1.8%) patients with mixed phenotype ALL. We also identify a group of 6 (3.7%) patients whose blasts were CD10 negative and showed B cell differentiation without surface membrane immunoglobulin. We conclude that age and phenotypic characteristics of ALL patients are mainly similar to ALL in the West but that L3 was much more common. A small group of six patients showed unusual B cell phenotype and require further evaluation and analysis.
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PMID:Immunophenotypic and age patterns of childhood acute lymphoblastic leukemia in Saudi Arabia. 238 75

Folylpolyglutamate hydrolase (folyl hydrolase) activity derived from murine tumors and various normal tissues was measured by means of high performance liquid chromatography using methotrexate polyglutamates as substrate. Enzyme-mediated hydrolysis was considerably greater (10-20-fold) on a specific activity basis in extracts from all normal mouse tissues (kidney greater than bone marrow greater than small intestine approximately equal to liver) than from tumor cells (Sarcoma 180 greater than Ehrlich approximately equal to L1210 cells). Enzyme preparations from purified absorptive and crypt cell epithelium from mouse small intestine exhibited comparable levels of specific activity and were greater than that derived from the total organ. Folyl hydrolase from mouse kidney showed mixed endo- and exopeptidase activity while that derived from all other normal tissues and tumor cells was consistent with endopeptidase activity. Levels of cell-free folyl hydrolase activity derived from tumor cells varied substantially with the phase of growth in vivo. Also, levels were appreciably lower from the same cells grown in vitro. Hydrolysis by crude or partially purified enzyme preparations from mouse small intestine or tumor cells conformed to Michaelis-Menten kinetics (single saturable component). Rates of hydrolysis and Km values were proportional to gamma-glutamyl chain length in the case of L1210 cell-derived enzyme but not for enzyme derived from small intestine. Km values derived for 4-amino-10-methylpteroyldiglutamate were the same [Km = 80.4 +/- 9 (SE) microM] for small intestine and L1210 cells. However, with 4-amino-10-methylpteroyltetraglutamate Km values were 3-fold lower for tumor cell preparations and 8-fold lower for preparations derived from small intestine. Fourfold lower Km values for 4-amino-10-methylpteroyldiglutamate were obtained with enzyme derived from Sarcoma 180 cells as compared to the enzyme from L1210 or intestinal cells. Varying levels of folyl hydrolase activity for methotrexate polyglutamates in cell-free preparations from different tumor cells appeared to reflect differences in in situ hydrolytic activity shown for the same substrate when internalized. The relevance of these results to antifolate pharmacology and, specifically, to a role for polyglutamates of 4-aminofolate compounds in determining cytotoxicity and selective antitumor activity of these agents is discussed.
Cancer Res 1986 May
PMID:Hydrolytic cleavage of methotrexate gamma-polyglutamates by folylpolyglutamyl hydrolase derived from various tumors and normal tissues of the mouse. 242 72

In the present study we have generated four new monoclonal antibodies (mAbs), termed SN5, SN5a, SN5b, and SN5c, which are directed toward the human common acute lymphoblastic leukemia antigen (CALLA). SN5 and SN5c were generated separately by immunizing two mice with a leukemia antigen preparation isolated from uncultured non-T-/non-B-acute lymphoblastic leukemia cells whereas SN5a and SN5b were generated by immunizing a third mouse with intact KM-3 (a cultured non-T-/non-B-acute lymphoblastic leukemia cell line) cells. It was found that the binding activities of mAbs SN5 and SN5c generated by using an isolated leukemia antigen preparation were approximately twice as large as those of mAbs SN5a and SN5b generated by using intact leukemia cells. All four of the present mAbs induced antigenic modulation of CALLA on the leukemia cells in vitro; subclasses of mAbs appear to be an important factor which influences the kinetics of antigenic modulation. SN5, SN5a, and SN5c immunoprecipitated a distinct Mr 100,000 component from detergent-solubilized cell membrane antigens but SN5b failed to do so. These four mAbs together with J5, another anti-CALLA mAb, were individually tested in a solid phase radioimmunoassay for reactivity with the detergent extracts of various human tissues, i.e., kidney, lymph node, spleen, brain, liver, pancreas, lung, and heart. SN5, SN5a, SN5c, and J5 showed reaction only with kidney whereas SN5b did not show significant reaction with any tissues including kidney. However, SN5b as well as SN5 showed a significant reaction with kidney in an immunoperoxidase-staining test. These results indicate that the interaction of SN5b with a unique epitope on the CALLA moleucle is strongly disturbed by relatively mild detergents (deoxycholate, taurocholate, and Nonidet P-450). These detergents did not significantly disturb the reaction between other mAbs (SN5, SN5a, and SN5c) and the corresponding epitopes on the CALLA molecule. Competitive binding experiments show that the three epitopes recognized by SN5, SN5b, and SN5c are sufficiently close to each other to allow complete or nearly complete reciprocal inhibition of binding to CALLA present on leukemia cells. Peculiar inhibition patterns, however, were observed between SN5a and the other three mAbs. SN5, SN5b, and SN5c inhibited only partially the subsequent binding of SN5a to the leukemia cells. Conversely, SN5a inhibited nearly fully the subsequent bindings of SN5, SN5b, and SN5c. These results suggest another unique epitope defined by SN5a.(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Res 1987 Apr 15
PMID:Unique epitopes of common acute lymphoblastic leukemia antigen detected by new monoclonal antibodies. 243 7

Circulating cerebriform lymphoid cells (Sezary cells) are considered to be highly predictive of cutaneous T-cell Lymphoma (CTCL). A leukemic peripheral blood (leukocyte count 24.5 x 10(9)/l) composed predominantly of cerebriform cells was found in a 75-year-old man presenting with weight loss and generalized lymphadenopathy but without skin lesions. Cell suspensions studies and immunohistochemistry of peripheral blood revealed that the cerebriform cells were B-cells (IgM+ Kappa+, HLA DR+, Leu 1+, CALLA-, B1+, and OKT 10+). A variety of T-cell markers (other than Leu1) was negative. Computer-assisted morphometry confirmed a nuclear profile typical of CTCL (mean nuclear contour index, 7.47). A lymph node that underwent subsequent biopsy revealed a follicular malignant lymphoma of small to intermediate cells with similar morphologic and immunologic characteristics to the circulating cerebriform cells. The findings of a leukemic presentation of a cerebriform B-cell lymphoma extends the recent observation of nodal B-cell lymphomas composed of cerebriform cells and indicates that circulating cerebriform cells should not be considered to be exclusively of T-cell origin.
Cancer 1988 Apr 15
PMID:Circulating cerebriform lymphoid cells (Sezary-type cells) in a B-cell malignant lymphoma. 245 Jun 33

The human breast cell line HBL100 acquires the capacity to invade normal tissues and to replace them by proliferation in vitro only at high passage levels (HPL). These cells therefore are a useful model for studying tumor progression in vitro. We have analyzed the expression of cell-surface markers supposed to be involved in the control of the neoplastic process. Quantitative flow cytometry has revealed that: (1) spontaneous expression of HLA class-I antigens strongly decreases in HPL HBL100 cells vs. LPL cells, which parallels amplification and over-expression of c-myc oncogene; (2) HLA DR antigens can be induced by IFN-gamma in LPL but not in HPL HBL100 cells; (3) HBL100 cells secrete a soluble protein factor which specifically inhibits HLA DR induction by IFN-gamma even in heterologous cell systems; (4) 50% of LPL HBL100 cells express integrin beta 3, whereas HPL HBL100 cells lose this antigen; (5) this cell line is myoepithelial in origin, since 100% of HBL100 cells exhibit the CD10 antigen. Our data stress a role of HLA antigens, of some integrins and of c-myc in the acquisition of malignant potential by myoepithelial mammary cells of the HBL100 line.
Int J Cancer 1989 Apr 15
PMID:Acquisition of tumorigenic potential in the human myoepithelial HBL100 cell line is associated with decreased expression of HLA class I, class II and integrin beta 3 and increased expression of c-myc. 249 51

Complementary DNA and genomic clones corresponding to the gene for the common acute lymphoblastic leukemia antigen (CALLA) were used to investigate the genetic structure and location of the CALLA locus. The gene, which encodes a 100-kDa type II transmembrane glycoprotein, appears to be a single copy locus of greater than 45 kb which is not rearranged in malignancies expressing cell surface CALLA. Cell hybrid analysis indicates that the CALLA-related DNA sequences are found on human chromosome 3. In situ hybridization studies reveal the regional location of the CALLA locus to be 3q21-27.
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PMID:The common acute lymphoblastic leukemia antigen gene maps to chromosomal region 3 (q21-q27). 252 Dec 37

The common acute lymphoblastic leukemia antigen (CALLA) is a 749-amino acid type II integral membrane protein expressed by most acute lymphoblastic leukemias, certain other lymphoid malignancies with an immature phenotype, and normal lymphoid progenitors. A computer search against the most recent GenBank release (no. 56) indicates that human CALLA cDNA encodes a protein nearly identical to the rat and rabbit neutral endopeptidase 24.11 ("enkephalinase;" EC 3.4.24.11). This zinc metalloendopeptidase, which has been shown to inactivate a variety of peptide hormones including enkephalin, chemotactic peptide, substance P, neurotensin, oxytocin, bradykinin, and angiotensins I and II, had not been identified in lymphoid cells. To determine whether CALLA cDNA derived from human acute lymphoblastic leukemia cells (Nalm-6 cell line) encodes functional neutral endopeptidase activity, we generated CALLA+ stable transfectants in the CALLA- murine myeloma cell line J558 and analyzed them for enzymatic activity in a fluorometric assay based upon cleavage of the substrate glutaryl-Ala-Ala-Phe 4-methoxy-2-naphthylamide at the Ala-Phe bond. Total lysates as well as whole-cell suspensions of the Nalm-6 line and of the CALLA+ transfectants, but not of the CALLA- J558 cells, possessed neutral endopeptidase activity. This enzymatic activity was associated with the cellular membrane fraction and was abrogated by the specific neutral endopeptidase inhibitor phosphoramidon. The unequivocal identification of CALLA as a functional neutral endopeptidase provides insight into its potential role in both normal and malignant lymphoid function.
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PMID:Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 ("enkephalinase"): direct evidence by cDNA transfection analysis. 252 88


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