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

A panel of monoclonal antibodies (mAbs) directed against B-cell and hairy cell leukaemia (HCL)-associated antigens was used to identify residual hairy cells in the peripheral blood and/or bone marrow samples from 20 patients with HCL, following treatment with interferon-alpha (IFN-alpha) or interferon-beta (IFN-beta). In all cases, hairy cells retained their characteristic phenotype, e.g. positivity for CD22, CD11c, CD25, CD32, and the HCL-associated trimeric protein (t-GP) recognized by the mAbs HML-1, B-ly7, LF61 and Ber-Act8. The most specific marker for identifying a small percentage of hairy cells in peripheral blood cytospins, was t-GP. In alkaline phosphatase/anti alkaline phosphatase (APAAP) stained preparations, t-GP+ hairy cells (provided with large cytoplasm and hairy surface) could be usually distinguished from t-GP+ normal lymphocytes (small-sized cells with smooth surface). In doubtful cases the percentage of residual hairy cells could exactly be estimated by double immunofluorescence staining for CD22 (B-cell marker) and t-GP. The rationale of the test is based on the finding that the small percentage (about 1%) of t-GP+ lymphocytes circulating in the peripheral blood of normal individuals are T-cells of the CD8 subset and not B-cells. The best markers for identifying residual hairy cells in routine bone marrow biopsies were CD45RA (mAb 4KB5) and CD20 (mAb L26). Immunohistological labelling was superior to morphological examination in picking up scattered hairy cells in bone marrow biopsies showing either severe hypoplasia or exuberant hyperplasia of normal haemopoietic series.
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PMID:Selection of a panel of monoclonal antibodies for monitoring residual disease in peripheral blood and bone marrow of interferon-treated hairy cell leukaemia patients. 170 9

The surface phenotype of neoplastic plasma cells from peripheral blood of plasma cell leukaemia patients and bone marrow of patients with myelomatosis was investigated with two monoclonal antibody panels including 50 selected from the B cell panel of the IVth International Workshop on Leucocyte Differentiation Antigens. The majority of myelomas expressed CD24 (HB8 epitope only), CD38, CD44, CD54, and the antigen recognized by the monoclonal antibody 8A. A range of other antigens may also be expressed including CD10, CD32 (FcR II), CD19, CD20 and MHC Class II. Antigens expressed by myeloma plasma cells can be considered in three groups: (a) antigens associated with lymphocyte and plasma cell differentiation: (b) antigens which are not lineage specific: and (c) molecules concerned with lymphocyte recirculation and intercellular adhesion (CD44 and CD54). The significance of CD44 and CD54 expression by plasma cells and the potential interaction of plasma cells with T lymphocytes and monocytes is discussed.
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PMID:Surface antigen expression of human neoplastic plasma cells includes molecules associated with lymphocyte recirculation and adhesion. 204 83

Two bispecific monoclonal antibodies (BsAb), differing in H chain isotype combination, were made for treatment of B-cell leukaemia/lymphoma; QAI-2, CD3-mouse-IgG1 x CD19-mouse-IgG2a and QAI-3, CD3-mouse-IgG1 x CD19-mouse-IgG2b. Both purified BsAb proved equally effective for their ability to target pre-activated T cells towards CD19 positive tumour cells. In T-cell proliferation assays, the capacity of Fc gamma RIa (CD64), Fc gamma RIIa-R131 and Fc gamma RIIa-H131 (CD32) transfected fibroblasts was tested to present the BsAb. The BsAb combining mouse (m) IgG1 and mIgG2a promoted T-cell activation in combination with the Fc gamma RIa transfectant; the mIgG1-mIgG2b BsAb was only marginally active. Both BsAb could not induce T-cell activation when presented by either of the Fc gamma RIIa transfectants. Similar results were obtained using PBMC cultures, containing Fc gamma RIa+/Fc gamma RIIa+ monocytes as accessory cells. The importance of Fc gamma R-dependent BsAb-mediated T-cell activation emerged from experiments with T cells and CD19 positive B-cell lines, showing that cross-linking via CD19+ target cells alone did not induce T-cell proliferation. Therefore, BsAb with functionally different Fc domains represent alternative strategies in BsAb therapy, the efficacy of which deserves to be compared in vivo.
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PMID:Evaluation of Fc gamma receptor mediated T-cell activation by two purified CD3 x CD19 bispecific monoclonal antibodies with hybrid Fc domains. 758 2

Stimulation of the CD40 antigen on normal B cells by crosslinking of anti-CD40 mAbs via their Fc receptor using a Fc gamma RII(CD32)-transfected mouse fibroblast cell line ('CD40 system') results in activation and proliferation. Not only normal B cells, but also malignant B cells fitting in the low-grade malignancy category such as chronic lymphocytic leukemia (CLL), hairy cell leukemia and follicular lymphoma could be induced to proliferation upon CD40 stimulation. Here, the 'CD40 system' has also been used to culture intermediate and high grade malignancies. Proliferation was measured by 3H-thymidine incorporation and cell counting after culture. Time curves showed that at day 7 most cultures were optimal. By flow cytometry, morphology and assessment of light chain restriction the monoclonal nature of the cultured B cells was proven. We confirmed that B cell malignancies with a more slowly evolving course, such as CLL (n=11), PLL (n=5), and low-grade NHL (immunocytoma and follicular cb/cc n=9), could successfully be cultured in the 'CD40 system'. In contrast, four out of seven cases of mantle cell lymphoma did not proliferate. Cases of precursor B lineage ALL (n=7), high grade NHL (n=3) and multiple myeloma (n=10) showed a heterogenous growth pattern. We conclude that the 'CD40 system', although not always successful, is a useful tool to culture a whole variety of B cell malignancies.
Leukemia 1996 Mar
PMID:Proliferation of B cell malignancies in all stages of differentiation upon stimulation in the 'CD40 system'. 864 67

The ability of pH-sensitive liposomes and immunoliposomes to deliver synthetic antisense oligonucleotides (oligos) into human myeloid and lymphoid leukaemia cells was examined. The cellular uptake of an 18mer anti-myb oligonucleotide encapsulated in liposomes was from three- to five-fold higher than that of 32P-oligos alone. In addition, anti-CD32 or anti-CD2 immunoliposomes improved the delivery of oligos to leukaemic cells carrying the appropriate receptor for the specific antibody-linked immunoliposome. The uptake of oligos was twice that of the liposome or non-specific immunoliposome encapsulated oligos. These findings support the use of liposomes or immunoliposomes to deliver antisense oligos into human leukaemic cells.
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PMID:Enhanced delivery of synthetic oligonucleotides to human leukaemic cells by liposomes and immunoliposomes. 900 50

A role for IgG molecules in the activation of human myelogenous leukemia cells was examined. When added to monoblastic (U937) leukemia cells, mouse (m)IgG1 produced a dose- and time-dependent inhibitory growth effect associated with the induction of morphological features characteristic of macrophage maturation, and enhanced surface expression of Mac-1/CD11b characteristic of monocyte development. A study of isotype dependency of mig indicated that the effect was specific for Ig molecules of the IgG1 and IgG2b subclasses, whereas IgG2a or IgM had no effect. In parallel to U937 cell maturation, a marked production of latent TGF-beta was observed in supernatants of leukemia cells cultured with mIgG1. Myeloblastic (HL-60) leukemia cell line similarly responded to mIgG1 or mIgG2b in induction of macrophage differentiation and in the absence of neutrophil differentiation. Human blood monocytes cultured in the presence of mIgG1, exhibited higher levels of IL-1 beta and IL-6 mRNAs associated with an increase in protein extracellular release, suggesting that the effect of mIgG1 on IL-1 beta and IL-6 production in human monocytes was mediated at both transcriptional and post-transcriptional levels. Monocyte activation by mIgG1 and mIgG2b was associated with increased cell surface expression of HLA-DR class II molecules. Human IgG1 (and to a lesser degree hIgG2), was also capable of inducing leukemia cell growth arrest and macrophage maturation whereas F(ab')2 fragments of mIgG1 were not as efficient as intact mIgG1 in blocking cell growth. Most importantly, mAbs reactive with Fc gamma RII (CD32-specific Abs 2E.1 and IV.3) blocked the effects of mIgG1 on leukemia cell proliferation. Taken together, these data indicate that binding of IgG1 molecules, possibly through Fc gamma RII, may generate an activation signal towards myelogenous leukemia cells and normal counterpart cells, ie monocytes, leading to induction of macrophage maturation and cytokine secretion.
Leukemia 1997 Apr
PMID:Induction of macrophagic differentiation and cytokine secretion by IgG1 molecules in human normal monocytes and myelogenous leukemia cells. 909 96

11q23 translocations (t(11q23)) are recurring cytogenetic abnormalities in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia, involving the same gene, ALL1 (or MLL). Mixed lineage antigen expression has been reported in these leukemias, but its frequency and clinical significance are unknown. We immunophenotyped leukemia cells from 19 adult de novo AML patients with t(11q23) by multiparameter flow cytometry. Translocations included t(6;11)(q27;q23), t(9;11)(p22;q23), t(9;11;19)(p22;q23;q13.3), t(2;11)(11;17)(q37;q11q23;q11), t(11;17)(q23;q25), t(11;19)(q23;p13.1), t(11;19)(q23;p13.3) and t(11;22)(q23;q11). FAB types were M4 and M5. The committed stem cell and myeloid antigens HLADr, CD4dim, CD11b, CD13, CD15, CD32, CD33, CD38 and CD64 were each expressed in 80-100% of cases, and the early stem cell and lymphoid antigens CD34, CD56, CD3, CD2 and CD7 in 42, 39, 16, 5 and 5%, respectively. Antigen expression frequencies did not differ from those in 443 adequately karyotyped M4 and M5 cases without t(11q23). Fifteen patients (79%) attained complete remission (CR); median CR duration and survival were 10.0 and 15.1 months. CR duration and survival did not correlate with antigen expression. In particular, patients with t(9;11) survived longer than those with other t(11q23) (median not reached vs 7.6 months; P = 0.048), but antigen expression did not differ in the two groups. Thus frequencies of lymphoid antigen expression are similar in AML with t(11q23) and in other FAB M4 and M5 cases, treatment outcome does not differ in t(11q23) cases with and without lymphoid antigen expression, and better outcome of patients with t(9;11) compared to other t(11q23) does not correlate with differences in antigen expression. Mixed lineage antigen expression is not a distinctive feature of AML with t(11q23).
Leukemia 1998 Mar
PMID:Acute myeloid leukemia with 11q23 translocations: myelomonocytic immunophenotype by multiparameter flow cytometry. 952 25

The bovine leukaemia virus (BLV) is a retrovirus that infects mainly B lymphocytes of cattle, but proviral DNA can also be isolated from monocytes/macrophages. This study investigated the effect of BLV infection on surface antigens on freshly isolated peripheral blood monocytes and cultured monocyte-derived macrophages, with and without lipopolysaccharide (LPS) stimulation. The effect of BLV infection on phagocytic activity of CD14+ monocytes was also assessed. The percentage of monocytes expressing the surface antigens CD11b, CD32 (FcgammaRII), MHC class II and the surface antigen recognised by mAb DH59B were increased in BLV-positive cattle. In contrast, expression intensity of all markers was low in samples from BLV-positive cattle. CD14+ monocytes from BLV-positive cattle showed less Fcgamma-receptor-mediated phagocytosis compared to monocytes from BLV-negative cattle. After 7 days in culture, there was evidence for shedding/downregulation of surface antigens on monocyte-derived macrophages, in particular on cells from BLV-positive cattle. LPS stimulation decreased the percentage of cells expressing the measured markers in monocyte-derived macrophages taken from BLV-negative cattle, but not in cultures derived from BLV-positive cattle. The results provide further evidence for an altered function of monocytes and macrophages in BLV-infected cattle.
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PMID:Analysis of the phenotype and phagocytic activity of monocytes/macrophages from cattle infected with the bovine leukaemia virus. 964 53

Recently, highly efficient natural killer-like T immunologic effector cells called cytokine-induced killer (CIK) cells have been described. Most interestingly, CIK cells have been shown to eradicate established human lymphoma cells in a severe combined immunodeficient (SCID) mouse xenograft model in vivo. The current study was aimed at increasing the sensitivity of leukemia and lymphoma cells to CIK cells. In particular, the authors wanted to target CIK cells to leukemia and lymphoma cells via reverse antibody-dependent cellular cytotoxicity. Binding of an anti-CD3 monoclonal antibody to CIK cell cultures derived from patients with lymphoma was shown using flow cytometric analysis. For the target side, several B-cell lines were found to express CD19 on the cell surface. There was an impressive increase in sensitivity to CIK-mediated lysis of various lymphoma and leukemia cell lines by preincubation of the targets with a monoclonal antibody against CD3. This increase could be partially blocked by preincubation with anti-CD16 (Fc receptor III) and anti-CD32 (Fc receptor II) antibodies. These data suggest that the increase in cytotoxic activity is caused by Fc receptor-mediated antibody binding. Cytotoxic activity could be further increased by adding an anti-CD28 antibody in addition to anti-CD3. Finally, there was a further increase in sensitivity to CIK-mediated lysis of CD19+ malignant cells using the bispecific OKT3xHD37 antibody with specificity against CD3 and CD19. Interestingly, preincubation of malignant cells with an anti-CD3 monoclonal antibody followed by addition of the bispecific OKT3xHD37 antibody led to a further increase of cytotoxic sensitivity compared with the addition of the bispecific antibody alone. In conclusion, these data suggest that cytotoxic activity of immunologic effector cells can be increased not only by using the bispecific antibody OKT3xHD37 in vitro but also by preincubation of CD19+ leukemia and lymphoma cells with a monoclonal antibody against CD3. In addition, the immunostimulatory effect of the bispecific antibody OKT3xHD37 can be further increased by adding a monoclonal antibody against CD3.
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PMID:Targeting of natural killer-like T immunologic effector cells against leukemia and lymphoma cells by reverse antibody-dependent cellular cytotoxicity. 1083 59

Experiments on the host cell spectrum of bovine leukaemia virus (BLV), a retrovirus closely related to the human T-cell leukaemia virus (HTLV), have yielded conflicting data. Currently, BLV is known to infect B cells, whereas its ability to infect other cell types, e.g. monocytes/macrophages, is doubtful. As monocytes/macrophages may have profound effects on the diversity of the T-cell response, we studied the possibility of in vitro infection, using bovine monocytes and SV40-transformed bovine macrophages. Proviral DNA was detected by nested polymerase chain reaction (PCR) from day 1 until the end of the experiments at either day 5 or day 80, depending on the quantity of virus used for infection. In addition, the infection was associated with morphological changes in infected cells as revealed by electron microscopy. The in vitro infection did not significantly change either the expression of surface antigens (CD11b, CD32, and major histocompatibility complex (MHC) class II) or the amounts of cytokine transcripts (interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, IL-6 and IL-12p40) with or without lipopolysaccharide (LPS) stimulation. The data suggest that BLV can infect monocytes, but the infection does not seem to influence the function or the phenotype of these cells. Infected monocytes may, however, play a role as a viral reservoir in vivo.
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PMID:Morphologic and functional changes in bovine monocytes infected in vitro with the bovine leukaemia virus. 1169 97


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