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

Evidence from correlative studies and Winn-type assays in syngeneic murine models has suggested that natural antibodies contribute to resistance against tumors in vivo. The B cell deficit associated with the X-linked immunodeficiency of CBA/N strain mice provided a genetic model in which to further test this question. RI-28, a radiation-induced T cell leukemia of the CBA/H strain acquired reduced levels of fluorescence-detected natural antibodies from the serum of X-linked immunodeficiency-bearing CBA/N and male (CBA/N x CBA/J) F1 mice compared with the serum from normals. Threshold s.c. inocula of the RI-28 appeared sooner and produced higher tumor frequencies in the X-linked immunodeficiency-bearing animals. This data coupled with the lack of correlating deficiencies in natural killer cell or activated macrophage activity provide the first genetic evidence for the hypothesis.
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PMID:Low natural antibody and low in vivo tumor resistance, in xid-bearing B-cell deficient mice. 278 60

Signals from many receptor-ligand interactions are mediated by enhancement of phospholipid hydrolysis which generates metabolic intermediates stimulating protein kinase C (PKC) and elevating cellular calcium. Pharmacologic agents such as phorbol 12, 13-dibutyrate (PDBu) and ionomycin selectively stimulate PKC and elevate intracellular calcium to directly stimulate downstream mechanisms critical to cell growth and function. This study examines the effects of PDBu, ionomycin, and rIL-2 on childhood ALL blasts of early B lineage with respect to various aspects of cell activation, including DNA synthesis, induction of non-MHC restricted tumoricidal activity, and changes in morphology and phenotype. Five childhood ALL samples were tested. A marked heterogeneity was seen among the ALL samples with respect to in vitro growth following manipulation with PDBu, ionomycin, and/or rIL-2, whereas normal peripheral blood lymphocytes (PBL) were consistently stimulated to grow with the combination of PDBu and ionomycin. Growth responsiveness did not appear to correlate with morphologic or phenotypic classification of the leukemia samples. Four of the five leukemia samples developed substantial non-MHC restricted cytotoxicity to K562 (natural killer cell (NK) sensitive) and Daudi (NK resistant) targets in response to rIL-2. This functional cytotoxic response correlated with morphologic changes in the cells and the appearance of granules. Phenotypic analyses of the ALL samples at the time of their peak cytotoxic function were consistent with the fresh ALL phenotype and showed no major change in cell populations. Three of the five ALL samples also retained rIL-2 induced cytotoxic capabilities when exposed simultaneously to the combination of PDBu and ionomycin, whereas rIL-2 induced tumoricidal activity in normal PBL and bone marrow cultures was inhibited by these reagents. These data show that morphologically and phenotypically similar ALL blasts have heterogeneous proliferative responses to the PKC and calcium modulators PDBu and ionomycin, as well as to rIL-2. Cytotoxic responses are also different from those of normal PBL and bone marrow cells with respect to kinetics and responsiveness to inducing agents. Thus current morphologic and phenotypic classifications of ALL may not adequately reflect the heterogeneity of this disorder as described here.
Leukemia 1989 Aug
PMID:Induction of tumoricidal activity and alterations of growth by interleukin-2 and manipulation of protein kinase C and cytosolic calcium in childhood acute lymphocytic leukemia cells. 278 55

A 74 year old woman with rheumatoid arthritis, hepatosplenomegaly, neutropenia, and peripheral blood lymphocytosis is described. The lymphocytes had a large granular morphology and expressed a CD3+ CD8+ Leu7+ surface antigen phenotype. They did not have natural killer cell function. Southern analysis of the lymphocyte DNA using two restriction enzymes showed a rearranged pattern for the T cell receptor beta chain gene, indicating a monoclonal lymphoproliferation. Large granular lymphocytosis is a rare and heterogeneous phenomenon, which has become more clearly characterised through the application of molecular biology techniques. Most cases appear to be forms of T cell leukaemia with a chronic benign course. The association between rheumatoid arthritis and large granular lymphocytosis is emphasised.
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PMID:Large granular lymphocytosis associated with rheumatoid arthritis. 284 61

Bone marrow-derived leukocytes of murine epidermis can express two phenotypes: typical Langerhans cells, which are Ia+ and Thy-1-, and a recently discovered second population that is Thy-1+ and Ia-. To verify that these phenotypes are expressed by two different cell types, and to help understand their lineage and function, we have studied morphology and reactivity with a large panel of antibodies. Dual antibody immunofluorescence combined with electron microscopy showed that Thy-1+ and Ia+ cells were each distributed in a regular fashion and formed adjacent dendritic systems in or close to the basal layer. Double-labeling studies with anti-Ia and a second monoclonal antibody revealed that all Langerhans cells expressed F4/80 (macrophage), Mac-1 (C3bi receptor), and 2.4G2 (Fc receptor), as well as the thymus leukemia (TL) and heat-stable (M1.69/16) antigens. A large fraction expressed S100 and all exhibited membrane ATPase and nonspecific esterase. In contrast, Thy-1+ cells lacked all these features of Langerhans cells, except that a minority were strongly reactive with 2.4G2. Thy-1+ cells also lacked differentiation antigens of most other types of leukocytes, except they were rich in asialo GM1. By electron microscopy, Thy-1+ cells had cytoplasmic granules that were similar in structure and in their aryl sulfatase content to those previously described in natural killer cells. The granules were enlarged in beige mice, suggesting a lysosomal origin, and were present in mast cell-deficient W/Wv mice, indicating no relation to mast cells. We conclude that Thy-1+ epidermal cells are thoroughly distinct from Langerhans cells. On the basis of morphology and phenotype, they may represent a type of tissue natural killer cell. Thy-1+ natural killer cells are now being identified in several nonlymphoid sites, such as gut epithelium and the livers of mice given adjuvants. If Thy-1+ epidermal cells prove to be natural killer cells, it is noteworthy that they represent a resident population regularly distributed in the basal layer of all mouse strains. The notion that Thy-1+ epidermal cells are immature natural killer cells is intriguing in light of recent evidence that Ia+ Langerhans cells are also immature with respect to accessory cell function. The epidermis may not have the functional capacities of a lymphoid organ, but it could contribute immature cells important for both natural and acquired resistance.
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PMID:The Thy-1-bearing cell of murine epidermis. A distinctive leukocyte perhaps related to natural killer cells. 286 Dec 45

In some infants with Down's syndrome, the circulating mononuclear population, when viewed with conventional and electron microscopy, contains many cells that closely resemble leukemic blast cells. In contrast with true leukemia, however, most of these infants with the "leukemia-like reaction in Down's syndrome" (LLR-DS) enter spontaneous remissions. We therefore investigated the natural resistance of such infants to hematological malignancy in vitro by means of natural killer cell assays. Mean natural killer cell determinations in four infants with LLR-DS were 17.5 +/- 9.2% and 37.6 +/- 18.5% against K-562 and Molt-4 target cells, respectively, at diagnosis. Later, during remission, these values were 34.3 +/- 14.3% against K-562 and 32.2 +/- 15.6% against Molt-4. The mean percentage lysis of Molt-4 both at diagnosis and during remission was greater (p less than 0.05) in LLR-DS than in children with acute lymphocytic leukemia and acute myelogenous leukemia at diagnosis. Natural killer cell activity levels in these LLR-DS patients were similar to levels obtained in other infants with Down's syndrome who were hematologically normal, as well as levels obtained in normal control specimens. Two of these LLR-DS patients progressively developed acute myelogenous leukemia with ultrastructural abnormalities several months later; one of these also developed another karyotype abnormality. Both remain in long-term remission exceeding 48 months.
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PMID:Natural killer cell activity and ultrastructure in myeloproliferative reactions in infants with Down's syndrome. 294 95

We report the immunological studies of 50 cases with a chronic progressive myelopathy associated with elevated antibodies to human T-cell lymphotropic virus type I (HTLV-I) and adult T-cell leukemia-like cells (HAM). These are as follows: (1) T-cell activation; (2) increase of the OKT4/OKT8 ratio, due mostly to increased inducer/helper T cells and/or decreased suppressor/cytotoxic T cells; (3) decrease of natural killer cell numbers and activity; and (4) increase of immunoglobulins (IgG, IgA). Our results provide evidence that autoimmune events may participate in the pathogenesis of HAM and may be relevant in the hypothesis of common immune mechanisms between HAM and HTLV-I positive tropical spastic paraparesis.
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PMID:Immunological studies of HTLV-I associated myelopathy. 297 11

Peripheral blood leukemia cells from patients with acute monoblastic leukemia (AMoL) were tested for killer cell activity against target cells that detected natural killer cell-mediated or monocyte-mediated spontaneous cytotoxicity. The fibrosarcoma cell line Wehi 164, pretreated with actinomycin D to induce susceptibility to lysis, specifically detects the activity of unstimulated human monocytes. In four of six cases of AMoL, high killer cell activity could be measured against this target. In three of these four cases, the killer cell activity could be assigned exclusively to the leukemic clone, based on the high leukocyte counts and the resultant dilution of normal cells, as evidenced by marker and by functional analysis. While leukemic cells with killer cell activity against Wehi 164 contained 34% to 45% cells that were positive for binding of the 63D3 monoclonal antibody, the two leukemic samples without killer cell activity contained only 1% and 12% 63D3-positive cells. Cell sorting of 63D3-positive and -negative cells from two leukemias with killer cell activity demonstrated that the killer cell activity was restricted to the 63D3-positive fraction of AMoL cells. These data demonstrate that monoblastic leukemia cells can be potent killer cells and that killing activity is linked to the 63D3-defined cell surface molecule.
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PMID:Killer cell activity of human monoblastic leukemia cells as detected with a monocyte-specific target cell. 315 90

The susceptibility of human myeloid and lymphoid leukemic blasts to the lytic action of recombinant interleukin-2 (rIL-2)-generated lymphokine activated killer (LAK) cells was analyzed. With the exception of the K562 cell line, all 9 leukemic cell lines tested were resistant to the natural killer activity of freshly isolated peripheral blood lymphocytes (PBL) from healthy donors but were susceptible to the lytic action of PBL cultured for 3 days in the presence of rIL-2. Of the 32 primary myeloid and lymphoid acute leukemia samples investigated, the great majority were natural killer cell-resistant but were variably sensitive to LAK effectors. Variations in LAK activity were observed according to the donor of PBL, while little or no difference was documented in the capacity to elicit LAK activity of PBL cultured with 100 or 1,000 U of rIL-2/ml. Pretreatment of the leukemic target cells with neuraminidase did not increase substantially their sensitivity to LAK activity. LAK cells generated from the PBL of patients at the onset of the disease or in complete clinicohematological remission lysed Raji cells as efficiently as normal LAK effectors. Finally, LAK cells were capable of abrogating the tumor growth in nude mice of a human leukemic T cell line. These findings demonstrate the susceptibility in vitro and in vivo of human leukemic blasts to the lytic effect of LAK cells and point to a possible clinical exploitment of this new form of adoptive immunotherapy in the management of acute leukemia.
Leukemia 1988 Jan
PMID:In vitro and in vivo susceptibility of human leukemic cells to lymphokine activated killer activity. 325 39

Peripheral blood and bone marrow mononuclear cells from 25 children with acute non-lymphoid leukaemia were analysed for natural killer cell activity and for cells with the Leu-7 and Leu-11b (CD 16) markers. Significantly reduced spontaneous cytotoxicity was detected in peripheral blood from children with untreated and active acute non-lymphoid leukaemia compared with that of the controls (P = 0.01 and P less than 0.05). Patients in remission, however, had normal natural cytotoxicity and normal numbers of Leu-7 and Leu-11b (CD 16)-positive cells. The natural killer cell activity in bone marrow from patients with untreated acute non-lymphoid leukaemia was also significantly reduced (P = 0.025). On the other hand, patients in remission had both an increased percentage of Leu-7 and Leu-11b (CD 16)-positive cells (P less than 0.05) and an increased natural killer cell activity (P less than 0.0005) in their bone marrow cells in comparison with the control group. This augmented natural killer cell activity is most probably a result of anti-leukaemic treatment. Stimulation with recombinant alpha interferon and recombinant interleukin 2 caused an increase in natural killer cell activity that was both significant and normal in both peripheral blood and bone marrow from children with acute non-lymphoid leukaemia.
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PMID:Altered natural killer cell activity in childhood acute non-lymphoid leukaemia. Augmented natural killer cell activity and cells expressing the Leu 7 and Leu 11b (CD 16) markers in the bone marrow of children in remission. 326 Oct 34

Clinical trials with bone marrow depleted of donor T lymphocytes indicate that both the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing bone marrow transplantation (BMT) for treatment of leukemia are greatly reduced. However, there has been a concurrent increase in the incidence of graft rejection, particularly among recipients of HLA-nonidentical marrow grafts. In order to investigate the nature of graft failure, peripheral blood mononuclear cells (PBMC) present at the time of graft failure have been characterized by phenotypic and functional analyses in 5 recipients of HLA-nonidentical marrow grafts. Rejection of HLA-nonidentical marrow grafts was associated with the emergence of host-derived T lymphocytes in all 5 patients. In 3 of these patients, the cells could be tested directly for cell-mediated cytotoxicity. Antidonor cytotoxicity was detected in each of these 3 patients. In one patient the target specificity of the cytotoxic lymphocytes was identified as the donor class I HLA antigen, HLA-B7. None of the patient PBMC mediated cytotoxicity against the natural killer cell target K562.
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PMID:Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia. Identification of host-derived antidonor allocytotoxic T lymphocytes. 329 49


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