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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E26 is an acute avian leukemia virus that contains two nuclear oncogenes, v-myb and v-ets, and that is capable of transforming early cells of the erythroid and myeloid lineages. In another study, we have found that TPA (phorbol 12,13-dibutyrate) treatment of E26-transformants displaying an 'early erythroid' phenotype results in the production of cells with either myeloid or eosinophil characteristics. To analyze this induction in greater detail we have produced a panel of four monoclonal antibodies against E26-transformants before and after TPA-induced differentiation. Two antibodies, MEP21 and MEP26, reacted with proteins of 150 and 47-60 kDa, respectively, which are expressed on the surface of E26 progenitor cells but whose expression is extinguished following TPA-induced differentiation. A third antibody, EOS47, recognizes a 100 kDa molecule that is expressed on the surface of TPA-induced peroxidase positive cells (an enzyme that in avian species is restricted to cells of the eosinophilic lineage). MEP21, MEP26, and EOS47 do not react with lymphoid, myeloid, or more mature erythroid lineage cell lines. The fourth antibody, MEP17, recognizes a heterodimer of 140 and 150 kDa chains which is expressed at high levels by E26-transformed progenitor cells and at lower levels by TPA-induced cells. Further biochemical characterization of the MEP17 antigen revealed a structure similar to that of the leukocyte adhesion molecule VLA-4; a member of the integrin family of adhesion proteins. All four antibodies react with subpopulations of cells in the bone marrow and spleens of 1-day-old chickens. Although the MEP21 and MEP26 antibodies do not appear to react with mature cells of most hematopoietic lineages they are expressed at high levels by mature thrombocytes. In addition, MEP17 is expressed at high levels by the majority of bursal B-cells, thrombocytes, and more weakly by thymocytes. The reagents described should be useful as markers for the study of development, migration, and differentiation of normal avian hematopoietic progenitor cells and eosinophilic precursors, and for the study of retrovirus-induced neoplasia.
Leukemia 1992 Oct
PMID:Cell surface proteins of chicken hematopoietic progenitors, thrombocytes and eosinophils detected by novel monoclonal antibodies. 140 65

VLA-1 to VLA-6 are cell-surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin. In addition, VLA-4 binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion prerogative for lymphocyte extravasation or 'homing'. Using frozen tissue of normal lymphoid organs and of 100 morphologically and immunologically typed B cell neoplasias, monoclonal antibodies to all six VAL-alpha and to the common beta-chain were applied to serial sections. VLAs were found differentially expressed in cytologically and microtopographically defined B-cell subsets [follicular mantle zone cells (MZ), follicular center cells (FC), extrafollicular cells (EF), and plasma cells (PC)] of normal spleen, lymph node, and thymic medulla (which contains an EF compartment). Thus, these cell types, which correspond to discrete stages of B cell development, can also be defined by their VLA status. Acute B lymphoblastic leukemia (ALL) was VLA-1-, 2-, 3 +/-, 4 +/-, 5 +/-, 6-. The VLA-1-, -2 +/-, 3+, -4+, -5+, -6-phenotype of chronic B lymphocytic leukemia (CLL) resembled that of MZ. Hairy cell leukemia (HCL) differed from CLL in its tendency to lack VLA-2, in its consistent lack of VLA-3, and altogether resembled splenic EF in its VLA profile. Mantle zone lymphoma (MZL) consistently expressed VLA-3 and -4 and frequently VLA-5. Nodal follicular center cell lymphomas (FCCL) were VLA-1- and -2- and very rarely expressed VLA-5 and -6. Thus, FCCL although roughly corresponding to FC, tended to aberrantly express VLA-3 and/or VLA-4. Burkitt's lymphoma resembled FCCL but expressed VLA-4 more frequently and at higher levels. Mediastinal clear cell lymphoma of B-cell type differed from FCCL in its regular lack of VLA-3, -5, and -6 and in frequently lacking VLA-4. Medullary plasmacytoma was VLA-1-, -2-, -3 +/-, -4 +/-, -5-, -6+, thus being the only B cell neoplasia which was consistently VLA-6+. With respect to the well-known clinical characteristics of the B cell malignancies examined, the leukemic phenotype might crucially depend on the presence of VLA-5.
Leukemia 1992 Apr
PMID:Adhesion molecules VLA-1 to VLA-6 define discrete stages of peripheral B lymphocyte development and characterize different types of B cell neoplasia. 158 89

Most of the circulating lymphocytes from three asymptomatic adults (one male, two female, age range 61-67 years) with isolated persistent lymphocytosis of between 7.1 and 10 x 10(9)/l possessed characteristic villous projections of the cell membrane. Morphological, histochemical, ultrastructural, immunological, and genotypic studies confirmed a clonal proliferation of tartrate-resistant acid phosphatase (TRAP)-negative CD5-CD10-CD25- and CD11c+ B-cells. In addition to CD11c, these cells expressed other adhesion receptors (LFA-1/CD11a, VLA-4/CD29/49d, ICAM-1/CD54, and LAM-1) and produced detectable amounts of interleukin-1 beta, interleukin-6, and in one case tumour necrosis factor-alpha mRNA. This monoclonal villous lymphocytosis (MVL) could be differentiated from B-cell chronic lymphocytic, prolymphocytic, and hairy cell leukaemias, and from previously recognized CD11c+ chronic B-cell leukaemia. A rare splenomegalic non-Hodgkin's lymphoma variant with circulating villous B-lymphocytes (SLVL), usually CD10+ and sometimes CD11c- and TRAP+, appears to be a closely related disorder. In all three patients the lymphocyte count increased very slowly, at a rate less than 5 x 10(9)/l per year, over 3-7.5 years of follow up, and a moderate splenomegaly eventually developed in one of the patients. Chemotherapy was never required. MVL may be a relatively benign clinical entity akin to SLVL within the group of CD11c+ B-cell lymphoproliferative disorders.
Leukemia 1991 Sep
PMID:Monoclonal lymphocytosis with villous lymphocytes: a chronic lymphoproliferative disease of CD11c+ B-cells. 168 36

Recently we reported the expression of the human natural killer cell associated antigen CD56 (Leu 19/NKH1) in plasma cells of a majority of multiple myeloma (MM) patients. CD56 is known to be an isoform of the human neural adhesion molecule N-CAM which is involved in homotypic adhesive interactions. By immunophenotyping using four CD56 specific monoclonal antibodies and immunoprecipitation analysis we here confirm that the Leu 19 antigen expressed by myeloma plasma cells is identical to N-CAM and corresponds to the 145 kDa isoform. Because of the possible biological role of adhesion molecules on myeloma cells, we compared the expression of N-CAM with the intercellular adhesion molecule 1 (ICAM-1) and the beta 1 and beta 2 integrins. By immunogold-silver staining of cytospin preparations of mononuclear cell suspensions, bone marrow plasma cells of 17 MM patients were analysed. Plasma cells expressed N-CAM (CD56) in 14 patients. ICAM-1 (CD54) in 16 patients, and beta 2 integrins (CD18) in eight patients. beta 1 integrins (CD29) were expressed in all patients. The expression of beta 2 integrins was always very weak while N-CAM, ICAM-1 and the beta 1 integrins showed a moderate to strong positivity. The plasma cells of five haematological normal individuals lacked significant N-CAM expression but were positive for ICAM-1 and both integrin subgroups. One plasma cell leukaemia patient and two out of four end-stage MM patients showed no expression of N-CAM or beta 2 integrins on their circulating plasma cells. Among 11 previously established myeloma cell lines, surface expression of ICAM-1 and the integrins was detected in most cases, while N-CAM was present in only four lines. Most cell lines showed coexpression of the fibronectin receptors (VLA-4 and VLA-5) and the laminin receptor (VLA-6). The collagen receptor (VLA-2) was not expressed. The N-CAM negative cell lines included four cell lines that were derived from plasma cell leukaemia patients. These results indicate that the expression of adhesion molecules is an intrinsic part of the biology of multiple myeloma.
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PMID:Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells. 172 26

We examined the effect of dibutyryl cAMP (dbcAMP) on the expression of LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), and VLA-4 (CD49/CD29) and on eosinophilic differentiation of a human leukemia cell line, EoL-1. Dibutyryl cAMP induced eosinophilic differentiation of EoL-1 cells from 6-9 days after the start of culture with down-regulation of CD11a, CD18, and CD49 expression and up-regulation of CD11b expression. Changes in integrin expression, except for CD18, were seen predominantly in the fraction containing eosinophilic granule-positive cells, suggesting that the changes were dependent on eosinophilic differentiation. On the other hand, dbcAMP-induced changes of integrin expression were reversible and were not seen on day 9 when dbcAMP was removed on day 3, whereas eosinophilic differentiation was still present. A combination of G-CSF and TNF-alpha, which also induced eosinophilic differentiation of EoL-1 cells, increased CD11b expression slightly but had no significant effect on the expression of the other integrins. Butyrate and PMA up-regulated CD11b expression without eosinophilic differentiation. The results collectively suggest that the regulation of integrin expression on EoL-1 cells is partly dependent and partly not dependent on eosinophilic differentiation. The possible involvement of protein kinase A and protein kinase C in these changes is suggested.
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PMID:Effects of cyclic AMP on expression of LFA-1, Mac-1, and VLA-4 and eosinophilic differentiation of a human leukemia cell line, EoL-1. 752 82

Most cases of acute lymphoblastic leukemia (ALL) arise from malignant transformation of B-cell precursors in the bone marrow. Recent studies have shown that normal and leukemic B-cell precursors bind to bone marrow stromal cells through the beta-1 integrins VLA-4 and VLA-5, thereby exposing early lymphoid cells to regulatory cytokines. It has been recently reported that the pre-B cell line NALM-6 is capable of migrating under layers of murine stromal cells in vitro (Miyake et al. J Cell Biol 1992;119:653-662). We have further analyzed leukemic cell motility using human bone marrow fibroblasts (BMF) as a stromal layer. The precursor-B ALL cell line NALM-6 rapidly adhered to BMF, and underwent migration or tunneling into BMF layers within 5 h, as demonstrated by light and electron microscopy, and confirmed by a chromium-labeling assay. Migration was also observed with the precursor-B ALL lines Reh and KM-3, with a T leukemia line RPMI-8402, the monocytic line U937, and the mature B line Daudi. In contrast, mature B (Raji), myeloid (K562, HL-60), and T lines (CCRF-CEM, MOLT-4) did not migrate. When cases of leukemia were analyzed, BMF migration was largely confined to precursor-B ALL, occurring in eight of 13 cases tested. Of other types of leukemia, migration was observed in one of four cases of T-ALL, but no evidence was seen in six acute myeloid leukemias and two patients with chronic lymphocytic leukemia. Only minimal migration into BMF was observed with purified sorted CD10+ CD19+ early B cells from normal adult marrow, while normal mature B lymphocytes from peripheral blood did not migrate. ALL migration was inhibited by monoclonal antibodies to the beta sub-unit of the VLA integrin family, and by a combination of antibodies to VLA-4 and VLA-5. Partial inhibition was also observed when leukemic cells were incubated with antibodies to VLA-4, VLA-5, or VLA-6 alone. In contrast, treatment of stromal cells with antibodies to vascular cell adhesion molecule or fibronectin (ligands of VLA-4 and VLA-5) did not prevent leukemic cell migration. These results indicate that ALL cells are highly motile and capable of rapid migration within marrow stroma, an effect largely mediated by VLA-4 and VLA-5. In the case of precursor-B ALL, this process may reflect a homing mechanism to areas of selective growth advantage within the bone marrow microenvironment.
Leukemia 1994 Oct
PMID:Migration of acute lymphoblastic leukemia cells into human bone marrow stroma. 752 99

Peripheral blood mononuclear cells (PBMCs) from 10 B-CLL patients were investigated after 24 hours of in vitro interferon-alpha (IFN-alpha) stimulation. The constitutional expression of the L-selectins (LECAM-1), LFA-1/CD11a, VLA alpha-4/CDw49d and ICAM-1/CD54 adhesion molecules was detected, and changes in their density after IFN-alpha stimulation were compared to results obtained by the high endothelial venule (HEV)-binding assay and a carbohydrate (phosphonomannan core polysaccharide: PPME and fucoidin) immobilization test. The LECAM-1 and ICAM-1 molecules were expressed on the great majority of CLL cells, while the LFA-1 and VLA-4 alpha-chains were expressed by only a small number of cells. Statistically significant changes (p < 0.001) were observed in LECAM-1 antigen density (changes in mean cell fluorescence), as well as in functional tests (HEV-, PPME- and fucoidin-binding; p < 0.01) after in vitro IFN-alpha stimulation. Based on a prior study (Jewell et al., Leukemia 1992: 6: 400-404) and on the present findings, not only an increased expression but also an enhanced function of the L-selectins seem to be well substantiated after IFN-alpha stimulation, which may explain the therapeutic effect of IFN-alpha in reducing the accumulation of leukaemic B cells in the blood. The remarkably high expression of ICAM-1 in this series necessitates further studies to clarify the exact expression rate and role of this molecule.
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PMID:Changes in adhesion molecule expression and function in B-cell chronic lymphocytic leukaemia after in vitro interferon-alpha stimulation. 753 38

The expression of the vascular cell adhesion molecule (VCAM-1), recently identified as cytokine-inducible ligand of the beta 1-integrin VLA-4, was investigated on normal and malignant haemopoietic precursors as well as on haemopoietic cell lines. VCAM-1 was demonstrated on > 20% blasts in 4/22 acute myeloid leukaemia (AML) and 6/10 acute lymphoblastic leukaemia (ALL) specimens but was absent from CD34+ normal bone marrow precursor cells. Interestingly, the VCAM-1+ AMLs classified as M1 and M5 simultaneously expressed N-CAM (CD56), a member of the immunoglobulin family. In ALL, VCAM-1 expression was restricted to Calla+ CD19+ precursors of the c-ALL subtype. VCAM-1 was also found on some cell lines, mainly of the B-lymphocytic type. Furthermore, in 13/20 chronic lymphocytic leukaemia (CLL) samples > 20% of the CD19+ B-lymphocytic precursors carried VCAM-1, which seemed to correlate with more advanced disease. Therefore VCAM-1 expression appeared to characterize leukaemic cells of the B-cell lineage as well as a CD56+ subset of AML. Since its expression was clinically correlated with dermal infiltrates of leukaemic cells in AML and with advanced Rai stages in CLL, VCAM-1 may play a role in enhanced adhesion of the malignant cells to tissues and/or to each other.
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PMID:The vascular cell adhesion molecule (VCAM-1) is expressed on a subset of lymphoid and myeloid leukaemias. 753 84

Interactions between hematopoietic cells and the stromal microenvironment are mediated by membrane-bound adhesion molecules. As the expression patterns of these molecules may alter the adhesive qualities of leukemic blasts, leukemic samples were investigated for the expression of beta 1-, beta 2-, beta 3-integrins, CD44, the three selectins and several members of the immunoglobulin family. CD44 (167/169), LFA-3 (158/169), the beta 1-integrins VLA-4 (120/123) and VLA-5 (45/51) and the beta 2-integrin LFA-1 (149/157) were found on > 70% of blasts in most cases of leukemias. Other molecules were restricted to specific differentiation stages and lineage. The beta 2-integrins Mac-1 (CD11b/CD18) and gp 150,95 (CD11c/CD18) were preferentially expressed on M4 and M5 subtypes, and NCAM (CD56) was only found on a subset of acute myeloid leukemias (17/113). Unexpectedly, the beta 1-integrins VLA-1 (1/51), VLA-2 (18/123), VLA-3 (5/43), VLA-6 (15/29) and the E-selectin (2/47) were expressed on > 70% blasts on a subset of leukemias of varied phenotype. These molecules were absent on normal CD34+ bone marrow precursors. The simultaneous analysis generally revealed a higher percentage of positive blasts in the blood than in bone marrow. Our observations therefore suggest that in leukemia these antigens are displayed on a non-adherent population that is defective and is unable to convert to an adherent, functionally active conformational state.
Leukemia 1995 May
PMID:Differential expression of adhesion molecules in acute leukemia. 753 15

In this study we have demonstrated that natural killer (NK) cells adhere to elements of the bone marrow stroma (BMS) including fibroblasts, fibronectin and laminin but not to collagen type I, vitronectin and hyaluronic acid. NK cells bind to fibronectin and laminin using the beta 1 integrins VLA-4 and VLA-5, and VLA-6 respectively. The mechanism of adhesion to bone marrow fibroblasts is more complicated with beta 1 and beta 2 integrins being partially responsible but the majority of adhesion remaining unexplained. IL-2 stimulation of NK cells resulted in an increase in the expression of adhesion molecules involved in binding of NK cells to bone marrow fibroblasts (BMF) and extracellular matrix (ECM) proteins including the beta 1 chain CD29, alpha chains of VLA-4 and 5, beta 2 chain CD18 and alpha L chain CD11a. A marked increase in expression of beta 7 was also observed. There was a significant increase in the adhesion of NK cells to fibronectin in response to IL-2 treatment. NK cells also bound more strongly to BMF following IL-2 treatment although the development of cytotoxicity appeared to interfere with the adhesion assay. NK cells competitively inhibit the binding of AML blasts but not ALL blasts to BMF. Mechanisms underlying the inhibition of leukemic growth by NK and LAK cells may include direct and cytokine mediated cytotoxicity and perturbation of the interaction of leukemic blasts with the bone marrow stroma which is essential for blast cell survival.
Leukemia 1995 Jun
PMID:Natural killer cells adhere to bone marrow fibroblasts and inhibit adhesion of acute myeloid leukemia cells. 759 92


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