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)

Tumor cells from six patients with immunoglobulin G (IgG) multiple myeloma were analyzed for surface antigens, cytoplasmic paraprotein, morphology, and response to various culture conditions. The tumor marker was the paraprotein idiotype. Low numbers of tumor cells were found in the blood of most of the patients. In some patients, the circulating tumor cells were solely B lymphocytes, whereas in other patients, they were lymphoid, lymphoplasmacytoid, and plasmacytoid. Dual surface antigen analysis of blood and bone marrow cells confirmed that the tumor may be composed of a spectrum of cell types. Thus, cells may range from surface-idiotype+,CD19+,CD20+, PCA-1-,cytoplasmic-idiotype- lymphocytes, to CD19-,PCA-1+,cytoplasmic-idiotype+ plasma cells that are surface-idiotype- or weakly surface-idiotype+. In one patient, some of the tumor cells co-expressed surface idiotype and CD10. The tumor B lymphocytes were activated in vitro to synthesize paraprotein by pokeweed mitogen (PWM), and by low molecular weight B cell growth factor (BCGF). In contrast, spontaneous synthesis of paraprotein by more mature tumor cells was inhibited by agents that also inhibit nonmyeloma plasma cells. These agents included PWM, gamma interferon, and phorbol ester. The results demonstrate that in multiple myeloma there exist different tumor cell types that are similar, by a variety of criteria, to normal B lineage cells at different stages of differentiation. Thus, further evidence is provided for the hypothesis of myeloma cell differentiation.
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PMID:Tumor cell heterogeneity in multiple myeloma: antigenic, morphologic, and functional studies of cells from blood and bone marrow. 278 20

Leukemic blasts from 40 consecutively admitted adults with untreated acute lymphoblastic leukemia (ALL) were examined for myeloid surface antigen expression. Of these, 14 (35%) were reactive with one or more myeloid monoclonal antibodies. Each example of myeloid surface antigen-positive (My+ ALL) met the standard morphologic and cytochemical criteria for ALL. In addition, none of the 13 samples studied for ultrastructural evidence of myeloperoxidase met the criteria for acute myelocytic leukemia (AML). All patient samples reacted with lymphoid monoclonal antibodies: CD10+ (8 patients), CD19+ CD10- (2 patients), T cell+ (2 patients), and T cell+ CD10+ (2 patients). Coexpression of myeloid and lymphoid determinants was established by two-color immunofluorescence studies using flow cytometry in five of five samples analyzed. Cytogenetic abnormalities that have been associated with myeloid and mixed leukemias were common, including t(9;22), 7q-, abnormalities of 11q with or without a translocation, 20q-, and -5. Blasts from seven patients were studied at the molecular level. Immunoglobulin heavy chain gene rearrangements were detected in five of five samples with B cell+ T cell- phenotypes. One sample that was T cell+ CD10+ was germline for the immunoglobulin heavy chain and the T cell receptor gamma- and beta-chain genes. The other patient with T cell+ CD10+ blasts relapsed with AML following allogeneic bone marrow transplantation. The leukemia cells at the time of diagnosis and the cells at relapse demonstrated similar cytogenetics and the same immunoglobulin gene rearrangement, suggesting a clonal relationship. As a group, the My+ ALL patients had a significantly decreased complete remission rate when compared to My- ALL patients. Further studies at the molecular level will be required to determine the significance of karyotype abnormalities in My+ ALL.
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PMID:Myeloid surface antigen-positive acute lymphoblastic leukemia (My+ ALL): immunophenotypic, ultrastructural, cytogenetic, and molecular characteristics. 281 78

The nature of translocation t(4;11) acute leukemia cells has been widely discussed over the past few years. Many authors report their phenotypic heterogeneity, ranging from apparently common acute lymphoblastic leukemia antigen-positive to monoblastic leukemia, through "promiscuous" phenotype. We studied in vitro phenotypic modulation of three typical cases after induction by 12-O-tetradecanoyl phorbol 13 acetate. The initial phenotype was different in each case, but all of them exhibited changes in morphologic shape, cytochemistry, and immunophenotype; common features appeared after induction by 12-O-tetradecanoyl phorbol 13 acetate, including esterase activity, expression of CD-9, CD-15, and CD-18 surface antigens, and monocyte/macrophage morphology. In all cases a B-associated surface antigen, CD-19, persisted. During clinical evolution, some previously reported cases have shown a karyotypic and phenotypic transformation. In one of our cases this phenomenon correlated with in vitro phenotypic modulation of initial blast population. Furthermore, clinical relapses and in vitro modulation always seem to evolve toward a more "mature" phenotype. Those results support the "promiscuous lineage" hypothesis, and point out the usefulness of in vitro studies to express the myeloid potential of this category of acute leukemia, which can be regarded as a model of early hematopoietic differentiation.
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PMID:In vitro study of translocation t(4;11) acute leukemia. Sequential range of phenotype. 291 3

In order to investigate the clinical significance of surface antigen analysis in acute myeloblastic leukemia (AML), the blasts from 196 patients with AML were analyzed prospectively with a panel of 16 monoclonal antibodies. The antibodies were selected to identify differentiation-associated antigens of either the myeloid lineage (MY9, PM-81, AML-2-23, MY7, MCS-1, MY8, Mo1, MY1, MY4, Mo2), T cell lineage (T101, T11), B cell lineage (B1, B4) or multiple lineages [J5 (CALLA), HLA-DR]. Independent morphological review and classification by French-American-British (FAB) criteria was performed in 161 of the 196 cases. One or more myeloid surface antigens were detected on the blasts of 195 cases, while B and T cell markers were detected on 0% to 2% of cases. When both blood and marrow samples were studied on the same patient, very few differences were noted between the antigenic profiles of the paired specimens. The frequency of expression of individual myeloid antigens ranged from 91% (PM-81) to 29% (Mo2). Expression of individual antigens was found to correlate significantly with several clinical parameters including FAB classification, cytochemical staining for alpha naphthyl acetate esterase, leukocyte count, and the presence of extramedullary disease at presentation. Two myeloid antigens (MY4 and MY7) predicted for a low rate of complete remission (CR) to standard induction chemotherapy. MY4+ cases (37% of the total population) had a CR rate of 53%, while M4- cases had a CR rate of 69% (P = .03). MY7+ cases (57% of the total population) had a CR rate of 55% while MY7- cases had a CR rate of 73% (P = .01). Neither MY4 nor MY7 antigen expression was correlated with patient age. Paired combinations of antigens were also examined. The [MY4- MY7-] phenotype was exhibited by 32% of all cases and was associated with an 82% CR rate while the CR rate of all other cases was 54% (P = .001). The expression of three antigens (HLA-DR, MY8, Mo1) was associated with a decreased continuous complete remission (P less than .05, median follow-up time of 19 months). Expression of MY8 antigen was also associated with decreased survival (P = .03). These results confirm earlier reports of antigenic heterogeneity in AML, and indicate that immunologically defined subgroups of AML patients which are of potential clinical significance can be identified.
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PMID:Use of surface marker analysis to predict outcome of adult acute myeloblastic leukemia. 294 31

The T1 surface antigen (CD5,p67) expression on blood lymphocytes (PBL) and lymphoid cells from lymph node biopsies (LN) from 31 patients with B-cell chronic lymphocytic leukemia (B-CLL) and 79 with B non-Hodgkin lymphoma (B-NHL), was detected in 25 B-CLL (80 per cent) and in 11 B-NHL (13 per cent) belonging to the following histologic subtypes: lymphocytic of CLL type (DLWD) one case, lymphoplasmacytoid (DLWD) four cases, centrocytic (DLPD) five cases, immunoblastic (DH) one case. All B-CLL and the T1 + B-NHL were also tested with monoclonal antibodies against the Common Acute Lymphoblastic Leukemia Antigen, B cells (FMC7, FMC8, BA1, Y29-55), T cells (OKT11a), HLA-DR and HLA-DQ monomorphic determinants. All the B-CLL and the T1+ B-NHL were CALLA-, BA1+, Y29.55+. FMC7+ cells were detected in large numbers six B-CLL (three T1+ and three T1-) and in four centrocytic lymphomas. FMC8 reacted with 70 per cent of leukemias (where it stained 30 per cent of neoplastic cells) and with 8/9 T+ B-NHL. HLA-DR and HLA-DQ molecules were detected in 100 per cent and 90 per cent of cases respectively. In vitro treatment of HLA-DQ- or T1- B-CLL with phorbol ester TPA led to the expression of these antigens as well as of the receptors for Interleukin 2 and MLR3 activation antigen. Surface membrane Ig (SIg) was detected in 79 per cent of cases, its density measured by FACS analysis varied, even markedly, from case to case. Among the B-CLL, cells with high SIg content were either T1+ or T1- and more likely FMC7+. The SIg- cases were seven B-CLL (five T1+ and two T1-) and two B-NHL, in which, however, cytoplasmic IgM was detected. This study reveals the existence of four major B-CLL subgroups: T1- SIg-, T1+ SIg+, T1+ SIg+, T1- SIg+. It also indicates that the T1 antigen may be transitionally present during B-cell differentiation and that its expression may precede that of SIg as supported by the in vitro studies. In addition, the finding that some B-NHL are T1+ suggests that they derive similarly to the B-CLL from a common progenitor.
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PMID:Expression of the T1 (CD5, p67) surface antigen in B-CLL and B-NHL and its correlation with other B-cell differentiation markers. 309 11

Identification of the antigens expressed on marrow B lineage cells can be used to develop a model for the sequential acquisition of cell surface antigens during B lymphocyte development. The data suggest that the surface antigen expression is highly controlled during the development of B cells with the coordinated acquisition of multiple cell surface antigens during the maturational process. The developmental scheme in figure 6 is inferred from the expression of cell surface antigens on single samples. Confirmation of the progression from one stage to the next requires the isolation of a particular stage with subsequent induction to the next stage in-vitro. These data suggest that the development of B lymphoid cells may be discrete rather than continuous. The most immature cells identifiable in the bone marrow express CD34+ as well as HLA-DR. The earliest recognizable B lineage cells (CD19+, bright CD10+) also express CD34+. These cells are smaller by forward light scattering when compared to the cells which express only CD34+ (precursor of myeloid cells). Cells within stage I also express TdT in the nucleus and are proliferating. As the cells progress from stage I to stage II, the B lineage cells lose cell surface CD34 and nuclear TdT. At this time the density of HLA-DR and CD45 increases while the amount of CD10 decreases. These changes occur with no detectable change in cell size as assessed by forward light scattering. HLA-DP is first detected on the cells at this time. The progression of cells from stage II to stage III is marked by the acquisition of CD20, HLA-DQ, and sIgM. The amount of CD45 increases further in the transition between stage II and stage III. The acquisition CD21 and CD22 as well as the loss of CD10 distinguishes stage IV from stage III. Once the cellular composition of normal marrow has been defined, perturbations from homeostasis can be identified. Since marrow is the tissue most sensitive to injury by most antineoplastic chemotherapy and radiotherapy regimens, a means of quantifying the changes from the normal state can provide an assessment of the cytotoxic injury produced in individual patients. By monitoring the return to normal, it may be possible to more precisely individualize therapy for each patient. With a clear understanding of normal hematopoiesis, it should also be possible to identify maturational blocks which occur in hypoplastic marrow states. This may provide a means of identifying the regulatory points for each lineage and provide strategies for overcoming the inhibition of development.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Flow cytometric analysis of normal B lymphoid development. 326 12

Four subpopulations of cells with different DNA content were present in the bone marrow of a pediatric patient with acute lymphoblastic leukemia. Flow cytometry of DNA/RNA and DNA/surface antigen expression enabled the identification and characterization of diploid, hypertriploid, tetraploid and hypertetraploid leukemic cells. This was not appreciated by cytogenetic analysis, which identified only some tetraploid cells (3/20 metaphases). Common acute lymphoblastic leukemia antigen was expressed in all aneuploid and also on 17% of diploid cells. Quantitative CALLA expression was unrelated to ploidy and cell size. Cellular RNA content paralleled ploidy, i.e. the more aneuploid cells had increased RNA content and there was pronounced RNA heterogeneity within each DNA stemline. The different subclones showed almost identical stages of early B-cell differentiation. The early pre B-cell antigens BL1 and BL2 were expressed in approx. 80 and 60%, respectively, of aneuploid leukemic cells. Cytoplasmic immunoglobulin heavy chain was also present. Clonal excess of lambda light chain immunoglobulin on the cell surface was present on less than 10% of hypertriploid, tetraploid and hypertetraploid leukemic cells indicating differentiation of a subpopulation of aneuploid leukemic cells to mature B cells. This was not seen for any diploid cells. The heterogeneity of the different subpopulations was also evident in the differences in response to chemotherapy: the hypertriploid and hypertetraploid subpopulations were most sensitive to initial induction chemotherapy.
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PMID:Common acute lymphoblastic leukemia characterized by four different DNA stemlines with heterogeneity in RNA content, antigen expression and sensitivity to chemotherapy. 345 78

The frequency and clinical significance of acute leukemia displaying both lymphoid and myeloid characteristics was determined in 123 consecutive children using a panel of lineage-associated markers. The leukemic blasts from 18 of 95 children (19%) with the diagnosis of acute lymphoblastic leukemia (ALL) by standard diagnostic criteria expressed myeloid-associated cell surface antigens. Despite immunological evidence of lymphoid differentiation (17 CALLA + and one T cell-associated antigen +) and findings of immunoglobulin gene rearrangement, blasts from these patients reacted with one to five monoclonal antibodies identifying myeloid-associated cell surface antigens (My-1, MCS.2, Mo1, SJ-D1, or 5F1). Dual staining with microsphere-conjugated antibodies and analysis by flow cytometry confirmed that some blasts were simultaneously expressing lymphoid- and myeloid-associated antigens. Conversely, blasts from seven of 28 patients (25%) with acute nonlymphocytic leukemia (ANLL), diagnosed by otherwise standard morphological and cytochemical criteria, expressed lymphoid-associated surface antigens. Dual staining of individual blasts demonstrated simultaneous expression of myeloperoxidase (MPO) (including Auer rods) in association with either T-11, CALLA, or terminal deoxynucleotidyl transferase. Blasts from one patient with ANLL demonstrated T cell receptor gene rearrangement, while blasts from another patient demonstrated characteristics associated with T (T-11), B (CALLA and heavy-chain immunoglobulin gene rearrangement), and myeloid (MPO) lineage. There were no consistent cytogenetic abnormalities, and no patient demonstrated independent leukemic clones. Each patient with typical ALL, except for myeloid-associated antigens, achieved complete remission with conventional induction therapy for ALL. By contrast, three of the seven children with ANLL whose blasts expressed the T-11 surface antigen failed ANLL induction therapy. These three patients subsequently achieved remission with ALL therapy.
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PMID:Acute mixed lineage leukemia: clinicopathologic correlations and prognostic significance. 393 24

CALLA is a 100,000-dalton surface glycoprotein expressed by malignant cells of patients with clinically important subtypes of acute leukemia. Incubation of human leukemic cells expressing CALLA with specific monoclonal antibody (J5) at 37 degrees C causes rapid and selective internalization and degradation of this antigen (antigenic modulation). In these studies we show that CALLA-specific monoclonal antibodies also identify a cell surface glycoprotein having a m. w. of approximately 100,000 on 2 to 6% of nonmyeloid nucleated cells of normal adult bone marrow, on normal fibroblasts in tissue culture, and on cells of several nonhematopoietic human tumor cell lines. J5 antibody similarly modulates the surface expression of CALLA on nonleukemic cell populations, although the extent of modulation at a given concentration of antibody varied considerably. Modulation was almost complete for CALLA on cells of normal bone marrow, but was highly variable for cells of nonhematopoietic cell lines, possibly reflecting variability in antibody access to surface antigen. Using fluoresceinated or iodinated J5 antibody to modulate expression of CALLA on cells of leukemic cell lines, we show that antibody-antigen complexes undergo a temperature-dependent redistribution on the cell surface during modulation to form microaggregates. Antibody as well as antigen is then internalized. Studies of [35S]methionine-labeled cells indicate that synthesis of CALLA continues despite modulation of its surface expression by specific antibody, implying that the presence of CALLA on the cell surface reflects a dynamic equilibrium between the processes of surface expression of newly synthesized glycoprotein and its spontaneous and antibody-mediated clearance. The implications of these observations for immunotherapy are discussed.
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PMID:Distribution and modulation of a human leukemia-associated antigen (CALLA). 622 2

Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual fluorescence techniques disclosed that these cells were heterogenous with respect to the expression of a series of differentiation and activation antigens defined by monoclonal antibodies. Thus, whereas all CALLA+ cells were Ia+ and expressed two activation antigens, J2 and T10, only 30-50% expressed B1 antigen. Furthermore, using methanol-fixed cells, it could be shown that approximately 20% contained intracytoplasmic mu chains (cyto-mu) and that approximately 15% were positive for the terminal transferase enzyme (TdT) marker. The CALLA+ fetal cells thus closely resemble the childhood acute lymphoblastic leukemia cell with respect to surface marker phenotype. A population of CALLA- cells devoid of mature erythroid and myeloid surface markers was found to contain higher numbers of TdT+ cells but lower numbers of cyto-mu, B1, and Ia+ cells than the CALLA+ subset. In vitro analysis of normal, purified CALLA+ cells demonstrated that incubation at 37 degrees C with J5 monoclonal antibody specific for CALLA resulted in the specific modulation of surface antigen. Similar results have previously been obtained with CALLA+ tumor cells. Although phenotypic analysis of CALLA+ cells suggests that these cells are relatively immature lymphoid cells, CALLA+ cells do not appear to contain either myeloid precursor cells (CFU-G/M) or the earliest lymphoid stem cells.
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PMID:Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA). 657 33


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