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D Delia

Publications and source records attributed to D Delia.

105 records · Page 6Linked to original sources

Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin.

A murine monoclonal antibody (OKT9) raised against human leukemic cells binds to a wide variety of leukemia and tumor cell lines and to a minority of leukemia cells taken directly from patients. Fetal thymus and liver are strongly reactive as are some normal, immature hemopoietic cells and activated lymphocytes. Reactivity with OKT9 appears to correlate with proliferation status in both normal and malignant populations. Biochemical analysis indicates that this structure is a approximately equal to 180,000-dalton glycoprotein with two disulfide-bonded subunits of approximately equal to 90,000-daltons. Isolation of the transferrin receptor from a T-cell line (MOLT-4) indicates that it also has a dimeric approximately equal to 180,000-dalton structure. Radio-labeled transferrin bound to its receptors can be specifically precipitated by the monoclonal OKT9, although the latter does not bind transferrin itself, indicating that the antigenic structure defined by this antibody is likely to be the transferrin receptor.

Animals↗

A monoclonal antibody specific for immature human hemopoietic cells and T lineage cells.

An anti-human monoclonal antibody (RFB-1) has been produced that reacts with a group of hemopoietic precursor cells in human bone marrow. These include terminal deoxynucleotidyl transferase-positive (TdT+) cells and myeloid colony-forming unit cells, functionally identifiable progenitor cells of the granulocytic-monocytic series. The expression of RFB-1 antigen on myeloid cells decreases as the cells become more mature; myeloblasts are weakly RFB-1+ but most promyelocytes are RFB-1-. RFB-1 also reacts with TdT+ thymic blast cells and cortical thymocytes but is unreactive with TdT- medullary thymocytes, although the majority of peripheral T cells are weakly RFB-1+. RFB-1 is the first anti-precursor cell reagent that labels human TdT+ cells in both the thymus and bone marrow as well as hemopoietic precursor cells but is unreactive with pre-B blasts and B lymphocytes.

Animals↗

Exploitation of monoclonal antibodies: a "who's who" of haemopoietic malignancy.

A library of monoclonal antibodies plus "conventional' markers (e.g. anti-TdT) have been used to explore the detailed phenotypes of leukaemic cells in relation to normal haemopoietic differentiation. This analysis reveals that consistent, composite phenotypes of different subclasses of lymphoid malignancies closely mimic those of corresponding normal cells at equivalent levels of maturation. It is suggested that three major target cell populations are available for lymphoid malignancy: the pluripotential stem cell (e.g. "lymphoid' blast crisis of CGL), lymphoid progenitors or stem cells in the bone marrow (non-T ALL) or thymus (T-ALL, T-NHL) and long lived, mature and immunocompetent T and B cells (T-CLL, PLL, Sézary and B-CLL, lymphoma respectively). The major phenotypes documented in different leukaemias represent the level of "maturation arrest' imposed on the dominant subclone; this is determined by, but not necessarily synonymous with, the "target cell' and associated clonogenic cell population in the leukaemia. No consistent major abnormalities of gene expression are revealed by this investigation and although they may exist (e.g. loss or acquisition of antigens with malignant progression) we suggest that they are irrelevant to the central issue of what alterations are essential and sufficient for the evolution of clonogenic leukaemic cells. We propose instead that subtle changes, which uncouple proliferation and differentiation, are all that is required.

Antibodies, Monoclonal↗

Isolation of human haematopoietic progenitor cells using monoclonal antibodies.

Studies of the differentiation of human haematopoietic cells have been greatly advanced by the use of in vitro cloning techniques to enumerate the myeloid and erythroid progenitor cells which form colonies in semi-solid medium. The granulocytic/monocytic colony-forming cells (CFU-GM) and erythroid burst-forming cells (BFU-E) are thought to be mononuclear cells, similar in size to medium size lymphocytes, but their ontogenetic relationship to other progenitor cells and the putative pluripotential stem cell remains obscure. This is partly because elucidation of parent-progeny relationships requires the isolation of precursor cells before they acquire mature phenotypic characters. Physical methods have failed to separate CFU-GM cleanly from other cells because of their heterogeneity, and immunologically specific markers for human progenitor cells have not been reported. We report here that a fraction containing all the granulocytic/monocytic and erythroid progenitor cells, as well as cells which may be lymphoid progenitors, can be isolated from bone marrow using a combination of monoclonal antibodies.

Bone Marrow Cells↗

A cell cycle study of the effects of Con A on synchronized mouse embryo fibroblasts: arrest at two specific stages of the cycle and dissociation between uptake of thymidine and DNA synthesis.

We have examined the effects of 50 microgram ml-1 of Con A added to synchronized mouse embryo fibroblasts at different times during the cell cycle. We found that Con A caused arrest of growth not solely by preventing G1-G0 cells from entering the S-phase but also by exerting a G2 block. We also found that Con A, which prevented commencement of S-phase, did not arrest cells already in S from reaching the G2 stage but inhibited the S-phase associated process of thymidine uptake. The inhibition was greater when the Con A receptors were extensively clustered.

Animals↗

Differentiation-linked expression of cell surface markers on HL-60 leukemic cells.

The cell surface antigenic phenotype of HL-60, a human acute promyelocytic leukemia cell line, has been analyzed before and after maturation induction with dimethylsulfoxide (DMSO) using a panel of markers including a "library" of monoclonal antibodies and "conventional" antisera in conjunction with the fluorescene-activated cell sorter. HL-60 cells express granulocyte and "leukocyte" differentiation antigens but not antigens of the lymphoid, platelet, and erythroid lineages. DMSO-induced morphological maturation was found to be associated with a decrease in the proportion of cells in mitotic cycle, induction of C3d receptors, increased expression of granulocytic and leukocyte antigens, and diminished expression of HLA-A,B,C and beta 2-microglobulin determinants. HL-60 cells have no detectable expression of HLA-DR-associated determinants as assayed by rabbit anti-p28,33 monoclonal anti-HLA-DR (monomorphic determinant), and HLA-DRw typing alloantisera. The relationship of these changes in cell surface properties to normal granulocytic differentiation is discussed.

Animals↗

Expression of the T1 (CD5, p67) surface antigen in B-CLL and B-NHL and its correlation with other B-cell differentiation markers.

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.

Antibodies, Monoclonal↗

Expression of differentiation and adhesion molecules in sporadic Burkitt's lymphoma.

The phenotypic features of 44 cases of sporadic Burkitt's lymphoma (BL) were investigated by monoclonal antibodies (MoAbs). The majority of cases were positive for HLA-DR (97 per cent), CD19 (100 per cent), CD20 (92 per cent) and CD37 (83 per cent) pan-B markers, in accordance with the B-cell derivation of the tumour; the B-cell restricted markers CD21, CD22 and FMC7 reacted with 28 per cent, 66 per cent and 75 per cent of cases, respectively. Of the mantle zone B-cell specific MoAbs, CD1c was always negative, whereas CD23 and 2.7 were positive with one and two cases, respectively. CD39 was weakly reactive on two specimens, one of which was CD23+. The germinal centre specific MoAbs CD10 and CD77 (Burkitt's lymphoma antigen) displayed a heterogeneous pattern of reactivity and allowed to identify 4 subgroups: CD10+/CD77+ (44 per cent), CD10+/CD77- (15 per cent), CD10-/CD77+ (36 per cent) and CD10-/CD77- (5 per cent). Of 15 cases tested for the expression of CD11a and CD18 lymphocyte-function-associated (LFA-1) antigens and their ligand ICAM-1 (CD54), seven were positive and six negative for the three markers, while the other two cases expressed alternatively the two molecules. Analysis of the putative normal BL cell counterpart, identified with the CD77 marker in normal lymphoid tissues, showed that all CD77+ B-cells were constitutively CD11a+/CD18+, suggesting that BLs are likely to arise from a LFA-1 positive B-cell and may down-regulate these molecules during neoplastic transformation.

Adolescent↗

Lack of TdT and immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease.

To study the pathogenesis of Hodgkin's disease (HD), which today remains obscure, we have undertaken a combined experimental approach: determination of TdT and molecular analysis of rearrangements of immunoglobulin heavy chain (IgH), T-cell receptor (TCR) beta chain and the T-cell rearranging gamma (TRG) genes. TdT determination indicate would the presence of immature cells that are not detected in the normal lymphnode; molecular analysis of the rearrangements of these genes would reveal the presence of even a small monoclonal population of both T and B lineages in the lymphnodes. We believe that the combination of these two types of analysis can indicate whether an expanding lymphoid clone is responsible for this disease. TdT determination was negative in all 41 cases tested. Gene rearrangements were studied in 10 cases for IgH and TCR beta genes and in 5 cases for the TRG gene. No abnormal band beside the germ-line ones was detected in any of our cases, ruling out the presence of a minor neoplastic population. We can explain these results in at least three ways: first, the neoplastic population could represent less than 1% of the total, thus escaping detection by current techniques; second, the neoplastic population is not lymphoid in nature or is composed of mature cells that do not rearrange Ig and TCR genes and therefore belongs to a true non-B, non-T lineage; third, the pathogenesis of HD is completely different from that of non-Hodgkin's lymphomas (NHL) and does not involve the clonal expansion of a cell frozen at a particular maturative stage as is thought to happen in most NHL.

DNA Nucleotidylexotransferase↗

Clinical and laboratory findings in a new case of leukocyte adhesion deficiency.

We describe a child suffering from recurrent bacterial infections whose cells exhibited laboratory findings compatible with the leukocyte adhesion deficiency (LAD) syndrome. Surface marker analysis with monoclonal antibodies (MAbs) to the individual alpha and beta chains of LFA-1/Mac-1/p150,95 antigens revealed that the patient's neutrophils did not express the common beta chain and LFA-1/p150,95 alpha subunits, but reacted weakly with four different MAbs specific for the Mac-1 alpha chain; however, no glycoprotein was immunoprecipitated from the patient's cells using the same anti-Mac-1 alpha MAbs. Functional analysis of the patient's phagocytes revealed many of the defects in adherence-dependent functions (adherence, chemotaxis and phagocytosis) described in patients with LAD. The studies performed on the phagocytes of the patient's relatives showed normal phenotypes and function, suggesting the possibility of a non heritable form of disease in this family.

Antigens, CD↗

Relevance of ultrastructural immunocytochemistry in the characterization of unclassifiable leukemias: correlation with phenotypic and genic studies.

Nine cases of acute leukemia presenting unusual phenotype were studied by light microscopy (LM) cytochemistry and transmission electron microscopy (TEM) immunocytochemistry with the immunogold staining (IGS) method; in addition, cytogenetic and molecular analyses were performed. The presence of myeloperoxidase (MPO) was studied at TEM in combination with immunophenotype to identify minor populations not characterizable at LM. Four of nine cases had no TEM/MPO reactivity, whereas the remaining five showed variable percentages of positive cells. Of the MPO negative cases, one was a megakaryoblastic leukemia with a positive platelet peroxidase (PPO) reaction, and three were lymphoid. Among the peroxidase positive cases, the percentage of MPO reactive cells was higher at TEM than at LM examination. In case 5 TEM analysis indicated that cells with some MPO reactivity at LM were non neoplastic myeloid cells. With this combined technique in cases 1 and 2 we excluded the presence of the MPO enzyme in CD15 positive lymphoid cells and, in another case, we documented the existence of CD19/MPO positive cells. The value of cytochemistry and immunology at the ultrastructural level for the characterization of blast cells and for the precise diagnosis of leukemia with "unusual" phenotype is illustrated.

Adult↗