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

As a model for lymphokine-activated killer (LAK) function in HIV infection, we studied LAK cells in cats infected with feline immunodeficiency virus (FIV), which causes an acquired immunodeficiency syndrome. Peripheral blood mononuclear cells cultured in concanavalin A and interleukin-2 developed LAK cytotoxicity against chronically FIV-infected CrFK cells and acutely infected CD4+ lymphocytes but not uninfected cells. LAK cells from FIV+ cats were more cytotoxic than LAK cells from uninfected cats. Enhanced FIV+ LAK cytotoxicity against feline leukemia virus-infected cells (FL74) suggested that the cytotoxicity was not antigen specific. Two-color fluorescence-activated cell sorter analysis and antibody depletion studies demonstrated that the majority of LAK cells and their progenitors were positive for both CD8 and CD57. The in vitro induction of dual positive CD8+CD57+ LAK cells was enhanced in FIV+ cats, as reported for HIV+ patients. These CD8+CD57+ LAK cells may play a role in maintaining the long asymptomatic stage of infection in FIV+ cats.
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PMID:Enhanced expression of novel CD57+CD8+ LAK cells from cats infected with feline immunodeficiency virus. 756 18

Expansion of the natural killer (NK) subset of lymphocytes represents a rare leukemia phenotype with variations in clinical presentation, morphology, surface phenotype, and effector function. This paper reports on a 5-year-old male patient who had an unusual presentation of an NK cell leukemia that was initially diagnosed as neuroblastoma. A bone marrow (BM) aspirate showed clumps of undifferentiated cells with the following phenotype: CD56bright+, CD33dim+, CD45-, CD2-, CD19-, CD16-, and CD57-. Cytochemistry was noncontributory. The patient, having failed to respond to conventional neuroblastoma chemotherapy, was subsequently diagnosed as having NK cell leukemia based on functional in vitro assays. The patient responded to acute lymphoblastic leukemia (ALL) chemotherapy but relapsed 4 weeks into treatment and eventually died 25 weeks after initial presentation. The cell surface phenotype observed is consistent with a rare NK cell subset, the biology of which has not been well defined. Freshly isolated BM cells killed K562 cells in a conventional 51Cr-release assay. Both interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) induced LAK activity against the Daudi cell line. IL-2 induced proliferation of the leukemic cells. TNF-alpha, IFN-gamma, IL-6, IL-1ra, and TGF-beta levels were assessed and found to be concentrated in BM, in contrast to plasma samples. TNF-alpha was present at a high concentration in BM (150.9 pg/ml), probably a reflection of the associated disease pathology of severe bone pain and pyrexia. In summary, this paper details clinical and laboratory investigations of a leukemia of a rare NK cell subset.
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PMID:Recognition of unusual presentation of natural killer cell leukemia. 757 92

We report a patient with acute large granular lymphocyte (LGL) leukemia, presenting as acute myelofibrosis (AMF). The leukemic cells were immature T-cells (CD5+, CD7+, CD16-, CD56-, CD57-, and CD41-), had monosomy 7, and secreted large amounts of Transforming Growth Factor-beta 1(TGF-beta 1). The serum levels of interleukins (IL)-2, -2R, -6 and -8 were elevated, while the IL-1 beta, IL-4, and tumor necrosis factor-alpha were normal.
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PMID:Cytokine profile in acute myelofibrosis associated with aggressive large granular lymphocyte leukemia. 763 82

In patients with primary immunodeficiencies the role of natural killer (NK)- and lymphokine (IL-2)-activated killer (LAK)-cells is not yet satisfactorily established. Using a clonogenic assay with K562 leukemia target cells, we studied their NK- and LAK-cell activity in vitro. Moreover, the effect of thymosin alpha 1 (T alpha 1) on LAK-cell activity was studied in 11 patients with different immunodeficiencies. The results were compared with data of healthy controls (n = 11) and cord blood samples (n = 6). Common variable immunodeficiency patients demonstrated a mean LAK-cell activity of about 65% of normal controls and cord blood samples. The moderately reduced LAK-cell activity was not affected by T alpha 1. In the immunodeficient other patients, low levels of LAK-cell activity with a mean value of 10% of normal controls were seen. The mean LAK-cell activity could be improved by T alpha 1: three patients showed an improvement of their LAK-cell activity up to 25-30% after T alpha 1 administration in vitro, but in one case T alpha 1 was without any effect. Analysis of the expression of the surface markers CD8, CD16, CD57 and CD8/CD57 revealed that only CD16 positive lymphocytes were significantly less in immunodeficient patients. We found a linear correlation between LAK-cell activity and CD8/CD57 double positive lymphocytes in all patients. Our results demonstrate that suppressed LAK-cell activity from immunodeficient patients can be individually improved by T alpha 1. Further in vivo studies should evaluate thymic peptide immunotherapy for individual immunodeficient patients.
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PMID:Thymosin alpha 1 effects, in vitro, on lymphokine-activated killer cells from patients with primary immunodeficiencies: preliminary results. 770 63

To date no hematopoietic progenitors of dendritic Langerhans' cells (DLC), which represent an highly efficient class of antigen presenting cells, have been identified or the cytokines they elaborate have been defined. Here we describe an acute leukemia patient whose blasts (90-96% in peripheral blood and bone marrow) had a phenotype consistent with putative progenitors of DLC. The patient was treated with ara-C and VP-16 but did not achieve remission. The blasts had lobulated nuclei, no cytoplasmic vacuolation or Auer rods and were weakly positive for acid phosphatase and non-specific esterase and negative for PAS, granzyme A, dipeptidyl aminopeptidase IV, ATPase/ADPase and lysozyme production. The blasts were positive for CD1a, CD4, CD16, CD35, HLADR, HLADQ, CD11b, CD11c, CD14, CD33, CD34, CD11a, CD71, CD19, CD25, IL-2R beta and negative for CD2, CD7, CD8, CD10, CD22, CD56, CD57, surface or cytoplasmic CD3, TCR delta and TCR beta, HTLV-1p19 and P-glycoprotein. On liquid culture with or without 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days, the blasts formed aggregates of proliferating and elongating cells on the wall of the flasks with a decline in CD34, numerous dendritic processes appeared on the cells and there was strong positivity for ATPase/ADPase, but no other changes in phenotype. No macrophages were observed, indicating derivation from separate DLCs. Cytogenetic analysis showed chromosomal abnormalities and electron microscopy showed Birbeck granules. Southern blotting of DNA showed rearrangement of one allele for both JH and TCR beta but no HTLV-1 related sequences. Culture supernatants from blasts cultured with or without TPA showed the production of large amounts of IL-8, IL-6, TNF-alpha, MIP-1 alpha, IL-10 and interferon gamma and modest amounts of IL-1 alpha, GM-CSF and stem cell factor. The presence not only of CD1a, HLADR, HLADQ and many other characteristics including Birbeck granules, but also differentiation along the lines of DLC with appearance of dendritic processes on the cells and expression of ATPase/ADPase activity, indicate that the leukemic blasts in our patient represented a leukemic counterpart of normal progenitors of DLC and the leukemia a new entity which could possibly be classified as AML-M8. Lastly, many pro-inflammatory cytokines produced by DLC could contribute to inflammation and IL-10 to immunosuppression.
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PMID:Phenotype, genotype and cytokine production in acute leukemia involving progenitors of dendritic Langerhans' cells. 791 55

A new NK cell line, designated as TKS-1, was established from the peripheral blood of a patient with large granular lymphocyte (LGL) leukemia which showed highly aggressive clinical course. The original leukemic cells, which had a surface phenotype of CD2+, CD3-, CD16-, and CD56+, proliferated well in the presence of 200 U/ml of interleukin-2 (IL-2). Morphologically, TKS-1 cells had immature nuclei and abundant cytoplasm with fine azulophilic granules. Surface phenotype of the cell line was CD2+, CD3-, CD16-, CD57-, and CD56-, CD56 antigen disappearing during the culture. Analyses of T-cell receptor (TCR) beta- and gamma-chain genes showed germ line configurations. Functionally, TKS-1 cells showed significant cytotoxicity against K562, Raji, and Daudi target cells. We consider that TKS-1 cells originated from CD16-negative immature type of peripheral blood NK cells. This cell line will be useful not only for the investigation of NK cell leukemia, but also for that of the mechanism of cytotoxicity mediated by normal NK cells.
Leukemia 1994 Nov
PMID:Establishment of a new natural killer (NK) cell line, TKS-1, from a patient with aggressive type of large granular lymphocyte (LGL) leukemia. 796 45

A 70-year-old man from an endemic area of human T-cell lymphotropic virus type I (HTLV-I) developed rapid generalized lymphadenopathy and abdominal tumours. The white blood cell count was 198.3 x 10(9)/l with 93% lymphocytes, 66.3% of which expressed large granular lymphocytes (LGLs). Bone marrow and lymph nodes were also infiltrated by LGLs. Surface markers were positive for CD4, CD25 and HLA-DR, and negative for CD3, CD8, CD16, CD56 and CD57. A monoclonal integration of HTLV-I proviral DNA was demonstrated on these LGLs by Southern blot hybridization analysis. This fact indicates that some adult T-cell leukaemia/lymphoma may morphologically present LGL leukaemia.
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PMID:Adult T-cell leukaemia/lymphoma featuring a large granular lymphocyte leukaemia morphologically. 819 30

We report a comprehensive study of a case of aggressive natural killer cell lymphoma/leukemia, which is characterized by young male predominance, rapidly progressive clinical course, and presence of lymphadenopathy, hepatosplenomegaly, and bone marrow involvement. The leukemic phase is frequently preceded by pancytopenia. The diagnostic clues are the detection of cytoplasmic granules in tumor cells on Wright-Giemsa-stained tissue imprints or smears and a selective loss of T-cell antigens. Immunophenotyping is decisive in making the final diagnosis by showing positive natural killer cell markers (CD16, CD56, and/or CD57), CD2, CD11c, and Ia, but negative CD3, T-cell receptor heterodimers, terminal deoxynucleotidyl transferase, and B-cell markers. Genotyping always shows germline configuration in both immunoglobulin and T-cell receptor genes. The unique feature in this case is its presentation as a testicular lymphoma, which has not been previously reported. Polymerase chain reaction was performed in this case but failed to detect human T-cell leukemia virus type I/II provirus. It is important to recognize this new entity as it is a highly aggressive disease with a rapidly progressive clinical course and fails to respond to any chemotherapeutic regimen available.
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PMID:Aggressive natural killer cell lymphoma/leukemia. A recently recognized clinicopathologic entity. 855 18

Cell line NKL was established from the the peripheral blood of a patient with CD3-CD16+CD56+ large granular lymphocyte (LGL) leukemia. The neoplastic LGL of this patient mediated natural killing and antibody-dependent cellular cytotoxicity (ADCC) and exhibited proliferative responses similar to normal CD16+CD56dim natural killer (NK) cells. The Morphology of NKL cells resembles that of normal activated NK cells. The karyotype of NKL is 47, XY, add (1) (q42), +6 del (6) (q15 q23), del (17) (p11). NKL cells express CD2, CD6, CD11a, CD26, CD27, CD29, CD38, CD43, CD58, CD81, CD94, CD95, class II MHC, and the C1.7.1 antigen, but do not express detectable levels of CD3, CD4, CD5, CD8, CD14, CD19, CD20, CD28, alpha/beta or gamma/delta T cell receptors on the cell surface. The density of the CD16, CD56, and CD57 antigens declined markedly on NKL cells during prolonged im vitro culture. Nevertheless, NKL cells can mediate ADCC as well as natural killing. NKL cells are strictly dependent on interleukin-2 (IL-2) for sustained growth and die if deprived of IL-2 for more than 7 days. NKL cells proliferate in response to concentrations of IL-2 as low as 1 pM, but an optimal proliferative response requires approximately 100 pM IL-2. NKL cells growing in the presence of IL-2 express abundant IL-2R alpha with little or no detectable IL-2 beta or gamma chain on the cell surface; NKL cells deprived of IL-2 express high levels of both IL-2R alpha and beta. IL-4, IL-7, and IL-12, unlike IL-2, do not maintain the viability of NKL cells. Furthermore, IL-1, IL-4, IL-6, IL-7, IL-12, tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha) and IFN-gamma do not support the growth of NKL cells. The NKL cell line may prove useful for studies of human NK cell biology.
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PMID:Characterization of a cell line, NKL, derived from an aggressive human natural killer cell leukemia. 859 69

The platelet-type thrombin receptor was expressed by large granular lymphocytes (LGLs) in a variety of proliferative diseases. Twenty patients with LGL proliferative disease were examined, including five T cell clones and a variety of polyclonal proliferations, some secondary to rheumatoid arthritis and Felty's syndrome; 17/20 showed high number of CD3+, CD8+, and CD57+ lymphocytes and 9/20 also had high numbers of CD16+ or CD 56+ positive lymphocytes. The thrombin receptor was present on more than 20% of the LGLs in 13/20 patients. The clonal T cell expansions showed the highest receptor expression with greater than 75% cells positive. Regression analysis of all 20 cases showed striking and highly statistically significant positive Spearman rank correlation between the proportion of thrombin receptor and CD57-positive LGLs (r = 0.56, P = 0.009). A negative correlation with CD56 was also found (r = -0.46, P= 0.043). Dual antibody flow cytometry showed the receptor was more often co-expressed with CD57 (64%) than with CD16 (19%) or CD56 (11%). The expression of the platelet-type thrombin receptor by LGLs of this phenotype raises the possibility of a functional role for thrombin in the pathogenesis of LGL proliferative diseases.
Leukemia 1996 Apr
PMID:Analysis of the platelet-type thrombin receptor in 20 cases of large granular lymphocyte proliferations. 861 48


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