Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the expression of CD56 (a neural cell adhesion molecule, NCAM) and CD57 in various hematopoietic and non-hematopoietic malignant cells, using Leu-19 and Leu-7 monoclonal antibodies. Although both molecules are commonly defined as a natural killer cell marker, we found that CD56 was highly expressed on blasts from patients with acute monocytic (4/6) and megakaryocytic (3/3) leukemias. In the latter, FACS two-color analysis revealed that leukemic megakaryoblasts simultaneously expressed CD56 and platelet-related antigens. Among leukemic cell lines, one myelocytic, three monocytic, and two megakaryocytic lines were positive for CD56. On the other hand, except for one large granular lymphocytic leukemia and one multiple myeloma cell line, none of the lymphoid leukemia cell lines or lymphoblasts from patients with acute lymphocytic leukemia (ALL) (0/15), non-Hodgkin's lymphoma (NHL) (0/2), and central nervous system (CNS) leukemia (0/2) reacted with Leu-19 antibody for CD56. The expression of CD56 in leukemia cells was not significantly affected by 12-O-tetradecanoylphorbol-13-acetate (TPA). By contrast, all hematopoietic materials were negative for CD57, while non-hematopoietic neuroblastoma cell lines expressed this molecule (4/5) as well as CD56 (5/5). Cytogenetically, the NCAM gene is located at chromosome 11q23, and chromosome breaks were often observed at this location in various leukemias. Blasts from all five acute non-lymphocytic leukemia (ANLL) patients and cell lines with 11q23-proximal chromosomal breaks were positive, while those from one ALL patient with an 11q23 abnormality were negative for CD56, necessitating further studies to clarify the link between the 11q23 abnormality and CD56 expression.
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PMID:Expression of CD56/NCAM on hematopoietic malignant cells. A useful marker for acute monocytic and megakaryocytic leukemias. 172 53

This report describes a patient with a large granular lymphocyte leukaemia (CD8 + lymphoproliferative disease) and severe neutropenia (less than 0.5 x 10(9)/l) in whom exercise resulted in a marked lymphocytosis, a phenomenon which has not previously been recorded. The lymphocyte count at rest was within normal limits (2.2 x 10(9)/l), then fell to the resting level within 15 min of cessation of exercise. The peripheral blood mononuclear cells showed the morphology of large granular lymphocytes (LGL) by light and electron microscopy both at rest (30%) and to a much greater extent during exercise (70%). Immunophenotyping of these lymphocytes during exercise demonstrated that the predominant cell was CD3+, CD8+, CD57+ (Leu7)/CD4-, CD16-, CD25-. In the resting state, despite a total lymphocyte count within the normal range, surface marker studies indicated an excess of cells with the CD8+/CD57 + T cell phenotype (26%; cf. normal range less than or equal to 10%). Functional assays revealed a minimal increase in natural killer (NK) activity during exercise. T cell receptor beta chain gene rearrangement was demonstrable in the peripheral blood at rest and during exercise. Although severe neutropenia was present, the growth of normal colony forming units, granulocyte-macrophage (CFU-GM) was not inhibited by patient lymphocytes and no anti-neutrophil antibodies were demonstrated. Finally, hyposplenism has developed and the relationship of this to the LGL leukaemia is discussed. In summary, the findings demonstrated large granular lymphocyte leukaemia as the primary disorder for which the primary manifestation, apart from the neutropenia, was a marked exercise-induced lymphocytosis.
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PMID:Exercise-induced CD8 lymphocytosis: a phenomenon associated with large granular lymphocyte leukaemia. 211 72

In the current study we used the therapy of established murine leukemia to identify the lymphocyte subsets responsible for toxicity and for therapeutic efficacy of high-dose IL-2. Initial results confirmed that high-dose IL-2 induces marked proliferation of a variety of host cells, including NK cells, Lyt-2+ T cells, L3T4+ T cells, and B cells. Infusion of antibody to NK-1.1 depleted NK-1.1+ cells in vivo and greatly reduced the toxicity of IL-2, but did not decrease therapeutic efficacy. By marked contrast, depletion of host T cells, either Lyt-2+ or L3T4+, had no effect on toxicity but greatly reduced therapeutic efficacy. The requirement for host T cells for the curative effect of IL-2 gives credence to the possibility that substantial efficacy of high-dose IL-2 against established malignancy may require existent host antitumor immunity. Since the human tumors that have been shown to have the most substantial responses to IL-2 (i.e., malignant melanoma and renal cell carcinoma) are those long considered to be immunogenic in the autochthonous host, the current study predicts that for these, as well as other immunogenic human tumors, it should be possible to decrease the toxicity and thus increase the therapeutic index of IL-2 by selectively depleting NK cells in vivo.
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PMID:Toxicity and therapeutic efficacy of high-dose interleukin 2. In vivo infusion of antibody to NK-1.1 attenuates toxicity without compromising efficacy against murine leukemia. 278 32

Two markers for cells in the growth fraction, the T9 antigen (i.e. the transferrin receptor) and the T10 antigen were investigated in frozen tissue sections of 105 non-Hodgkin lymphomas (NHL). The results were correlated with the histological subtype and the pattern of tumour infiltration by reactive cells. Special attention was directed to the density of natural killer (NK)-like cells using the anti-HNK1 (Leu7) antibody since the transferrin receptor (tfr) or other growth-associated membrane structures may serve as target for NK cells. Our study confirms a relationship between number of tumour cells with the T9 marker and tissue infiltration by HNK1+ cells in NHL of low (chronic lymphocytic leukaemia, hairy-cell leukaemia, immunocytic lymphoma, centroblastic-centrocytic lymphoma) and intermediate (centrocytic and centroblastic lymphoma) but not in NHL of high malignant grade (immunoblastic and lymphoblastic lymphoma). Comparable results were obtained with the T10 antigen although the correlation was less close. The percentage of cells in the growth fraction, defined by the expression of the T9 and T10 marker, corresponded with prognostically unfavourable subgroups with the remarkable exception of follicular NHL of centroblastic-centrocytic type. This lymphoma showed high numbers of cells with the T9 and the T10 marker in a microenvironment resembling normal germinal centres in many aspects.
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PMID:Growth fraction of tumour cells and infiltration density with natural killer-like (HNK1+) cells in non-Hodgkin lymphomas. 300 54

Age-related changes in glucuronidation may potentially lead to a decrease in excretion of reactive compounds, resulting in enhanced toxic effects. 4,4'-Thiobis(6-t-butyl-m-cresol) (TBBC), a major antioxidant in the rubber industry, was selected as a model compound to evaluate glucuronidation as a function of age because it is directly conjugated to UDP-glucuronic acid (UDPGA) without requiring oxidative metabolism. To assess glucuronidation changes in vivo, male F344 rats, 2.5, 16, and 26 months of age, were administered 5 mg [14C]-TBBC/kg (10 microCi/kg) iv and urine and feces were collected for 3 days. Bile was also collected for 6 hr from animals of the same age groups after iv doses of 5 and 25 mg/kg [14C]TBBC. Total radioactivity was determined in all samples and the profile of metabolites in bile analyzed by HPLC. Along with a decrease in the older animal's ability to excrete TBBC-derived radioactivity in bile, feces, and urine, there was a decrease in the percentage of the dose eliminated in bile as glucuronide. In vitro, the microsomal glucuronyltransferase activity using TBBC as a substrate decreased in the senescent animals. The hepatic concentration of the cofactor UDPGA also decreased from 2.5 to 28 months of age. The apparent Vmax for the enzyme decreased as a function of age while the apparent Km decreased for the substrate (TBBC) but not for the cofactor (UDPGA) in the 26-month-old rats. These data suggest that with the decrease in the activity of the enzyme as well as a decrease in the available UDPGA, the ability of the senescent rats to conjugate and excrete TBBC may be altered. Thus, the in vitro decline in TBBC glucuronidation is compatible with the decreased excretion of TBBC-derived radioactivity observed in vivo in old rats. When toxicity was evaluated in 2.5-, 16-, and 26-month-old rats exposed to 0.25% TBBC in their diet for 14 days, no age-related change in the toxicity of TBBC was observed. However, there appeared to be an increase in leukemia in the treated senescent rats.
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PMID:The effect of age on the glucuronidation and toxicity of 4,4'-thiobis(6-t-butyl-m-cresol). 312 43

We have reported that immunization of H-2k mice with lymphoid cells from various allogeneic strains induced a population of cells that could eliminate first-passage spontaneous AKR leukemia from the spleens of immuno-suppressed AKR (H-2k) hosts. In the present study, we examined the nature of the cells responsible for this graft-vs-leukemia (GVL) reaction and compared them to cytolytic cells detected in vitro. Spleen cells from alloimmunized CBA/J (H-2k) mice were selectively depleted of various subpopulations by treatment with antibody and complement (C), then tested in vivo for GVL reactivity. Cell suspensions depleted of Thy-1.2+, Lyt-1+, or Lyt-2+ lymphocytes had no significant GVL reactivity, whereas suspensions depleted of NK-1.2+ cells retained GVL reactivity. The GVL-reactive cells persisted in H-2-compatible donor mice for up to 56 days. Lyt-1+2+ lymphocytes that were cytotoxic for cultured AKR leukemia cells in vitro could be detected in the spleens of alloimmunized H-2-compatible mice after expansion of the cells in T cell growth factor. Using quantitative limiting dilution cytotoxicity assays, we found that the frequency of leukemia-reactive cytotoxic lymphocytes (CL) in the spleen showed a direct correlation with the GVL efficacy of the cells in vivo. Alloimmunization was essential for induction of the GVL-reactive cell population. CL in alloimmunized mice consisted of heterogeneous cytotoxic specificities; i.e., some CL were leukemia-specific, others lysed only nonleukemic AKR target cells, and a third group mediated killing of both leukemic and nonleukemic target cells. The CL appeared to be H-2 restricted and specific for non-H-2 antigens shared by the AKR leukemia and the alloimmunizing cells.
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PMID:Characterization of alloimmunization-induced T lymphocytes reactive against AKR leukemia in vitro and correlation with graft-vs-leukemia activity in vivo. 619 24

Preincubation of tumor cells with actinomycin D (Act D) rendered various murine and human lines susceptible to killing by unstimulated human peripheral blood mononuclear cells (PBM) in a 6-hr 51Cr-release assay. The murine WEHI 164 sarcoma was selected for analysis of drug-dependent cellular cytotoxicity (DDCC) because high levels of killing were detected with this tumor, and it was considerably resistant to natural killer (NK) cell activity. Optimal conditions for induction of susceptibility to lysis included a 3-hr preincubation with 1 microgram/ml Act D. Effector cells of cytotoxicity against Act D-treated WEHI 164 cells were plastic adherent (greater than 85% monocytes). Cells nonadherent to plastic and nylon wool (less than or equal to 1% monocytes) had no appreciable DDCC activity. In contrast NK activity against K562 cells was mediated by nonadherent cells. When PBM were fractionated on a one step discontinuous gradient of Percoll designed to enrich for monocytes (greater than 90% pure), DDCC activity was found in the monocyte fraction, and the lymphoid cell-enriched fraction had no cytotoxicity against Act D-treated WEHI 164 cells. In contrast, NK activity against K562 was recovered with lymphoid cells, and monocytes had no NK cytotoxicity. Upon fractionation on a six step Percoll gradient designed to enrich for large granular lymphocytes (LGL), the denser lymphocytes (fraction 4-6) and the less dense LGL with NK activity (fraction 2-3) had no cytotoxicity against Act D-treated WEHI 164 sarcoma cells. DDCC activity sedimented in fraction 1 in association with monocytes. PBM were fractionated according to monoclonal antibody-defined surface markers by using a fluorescence-activated cell sorter. Effector cells of DDCC were positive for monocyte markers (Mo2, UCHM1) and were negative for NK cell (B73.1, HNK1), T cell (T11), and B cell (Leu-10) markers. Macrophages obtained by culturing blood monocytes in vitro for 5 to 10 days had DDCC activity. Similarly, peritoneal and bronchoalveolar macrophages had considerable cytotoxicity against Act D-treated target cells, whereas minimal or no NK activity was found at these anatomic sites. Cells of human or murine origin, preincubated with Act D for 3 hr, were heterogeneous in their susceptibility to monocyte killing in a 6-hr 51Cr-release assay. High levels of cytotoxicity were observed with the murine WEHI 164 sarcoma and 3T3 "fibroblast" line and with the human CEM leukemia. Monocytes were weakly (but significantly) cytotoxic against the ALAB breast carcinoma (human) and the 8387 sarcoma (human).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Rapid killing of actinomycin D-treated tumor cells by human mononuclear cells. I. Effectors belong to the monocyte-macrophage lineage. 669 Jun 24

A 66-year-old male patient was admitted with dyspnea; physical examination revealed petechiae and systemic lymphadenopathy. Laboratory findings showed leukemia. The blasts in the peripheral blood were negative for cytochemical myeloperoxidase, and had condensed nuclear chromatin with a nucleolus. The histological diagnosis of the biopsied neck lymph node was lymphoblastic lymphoma. The leukemia cells expressed CD2, CD6, CD7, CD13low, CD56, beta chain of IL-2 receptorlow (IL-2R beta), and HLA-DR antigens, but not other pan-T (CD5, CD3, CD4, and CD8); pan-B (CD10, CD19, CD20, and CD24); natural killer (NK) (CD16, CD57); or myeloid (CD33) antigens. Electronmicroscopy revealed convoluted nuclei with conspicuous nucleoli and peripherally condensed heterochromatin. Membrane-bound granules containing an electron dense matrix were observed in the cytoplasm, indicating the NK cell nature of the neoplastic cells. While terminal deoxynucleotidyl transferase (TdT) and cytoplasmic CD3 were not detected by immunofluorescence on fixed smears, Northern blot analysis revealed the gene expression of CD3 epsilon, CD3 zeta, and TdT. Gene rearrangement analysis revealed that the beta, gamma, and delta chains of T-cell receptor (TCR) and immunoglobulin heavy chain (IgH) were of germline genotype. While the overall interpretation of the phenotype and genotype was difficult, the derivation of an immature stage of NK lineage was strongly suggested, based predominantly on the electronmicroscopic features. Despite initially successful chemotherapy, the patient died 14 months after initial presentation.
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PMID:Novel leukemic lymphoma with probable derivation from immature stage of natural killer (NK) lineage in an aged patient. 753 82

Peripheral blood lymphocytes of 46 recipients of lymphocyte-depleted bone marrow allografts were phenotypically analysed over a period of 1 year. We investigated the repopulation of lymphocyte subpopulations and their relation with clinical parameters such as graft-versus-host disease (GVHD), graft-versus-leukaemia and cytomegalovirus (CMV) infection. The number of repopulated T cells varied strongly between the blood samples of the recipients. In 45% of the recipients the number of T cells recovered to or above normal levels within 3 months after bone marrow transplantation (BMT), whereas the other recipients remained below normal up to 1 year after BMT. In recipients with a high repopulation, the CD8+ T-cell subset contributed more to this high repopulation than the CD4+ T-cell subset. We showed that the majority of T cells of these recipients expressed the alpha beta T-cell receptor, CD8, CD57 and CD11b. HLA-DR was also highly expressed reflecting the activation stage of T cells in these recipients. BMT recipients with a high repopulation of CD8+ T cells showed a lower incidence of leukaemic relapse than recipients with a low repopulation. The 3-year probability of relapse was 19% versus 64% (P = 0.03), respectively. The relative high number of CD8+ T cells at 3 months after BMT was not associated with the incidence of GVHD. In contrast, occurrence of CMV infection after BMT was significantly higher in these recipients. Our results indicate that CD8+ T cells, predominantly CD57+, of BMT recipients with an expansion of these cells represent an in vivo activated cell population. This CD8+ T-cell population may consist partially of cytotoxic cells with anti-leukaemic activity as suggested by a low relapse rate. The signal for the strong expansion of these CD8+CD57+ T cells after BMT is still unclear, but association with CMV infection suggests that viral antigens are involved.
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PMID:Expansion of CD8+CD57+ T cells after allogeneic BMT is related with a low incidence of relapse and with cytomegalovirus infection. 754 Aug 55

The malignant proliferation of natural killer (NK) cells which are morphologically characterized as large granular lymphocytes (LGL) is a well known clinical entity which was named after its morphological appearance as LGL-leukemia/lymphoma. Similar to non-malignant NK-cells, these tumors can be divided into those which express the CD3-T-cell receptor complex and those which do not. The CD3-positive type of LGL-leukemia is immunophenotypologically characterized by the expression of CD16, and variably CD 56 and CD 57, and generally follows a more indolent course. In contrast, malignant proliferations of CD3-negative LGL express either CD16 or CD 56, and only occasionally CD 57 on their cell surface. Clinically, CD3-negative NK-lymphomas tend to progress rapidly. We report here the case of a high grade malignant lymphoma which was characterized by an immunophenotype typical for CD3-negative NK-cells (CD2+, CD3-, CD16+, CD56(+), CD57-). The disease proved to be rapidly fatal despite aggressive chemotherapy. Interestingly, the patient suffered from a high turn over pancytopenia, which also characterizes NK-cell leukemias/lymphomas of the LGL-type. However, our patient's lymphatic cells appeared highly immature, and cytoplasmic granules, characteristic for LGL-cells, could not be discerned either microscopically or electronmicroscopically. Furthermore, the malignant lymphatic population had the T-cell receptor beta-chain rearranged. We therefore concluded that our patient might have suffered from a malignant proliferation of a putative precursor cell intermediate between T-cells and NK-cells.
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PMID:High grade malignant lymphoma with clinical characteristics and immunophenotype of natural killer cells. 754 3


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