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

A 28-year-old male was admitted to our hospital because of hepatosplenomegaly and granular lymphocytosis. His peripheral leukocyte count was 3,000/microliters with 43% of granular lymphocytes (GL). These GLs were immunologically phenotyped as CD2+CD3-CD4-CD8-CD16+CD56+HLA-DR+ and were found that TcR genes coding beta and gamma chains were not rearranged. Chromosomal analysis of his GLs stimulated with IL-2 showed 47 XY, +8. This patient was diagnosed as a granular lymphocyte leukemia of natural killer cell type. Blood chemistry showed elevation of serum GOT, GPT and LDH values. The fever persisted until administration of prednisolone was initiated. But 40 days after, high fever appeared again and the liver and spleen were extremely enlarged. Combined chemotherapy was then started but resulted in no effects. He died of hepatic failure on the 77th day from admission. 47 XY, +8, that has been reported in acute non-lymphocytic leukemia and myelodysplastic syndrome, may be related to the pathogenesis in some cases of granular lymphocyte leukemia.
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PMID:[Granular lymphocyte leukemia of natural killer cell type; association with 47 XY, +8 by interleukin 2 (IL-2)-stimulated chromosomal analysis]. 225 62

Understanding the biology and treatment of various cancers (including leukemia) and immunodeficiency disorders is still an ongoing and experimental process. Animal models have been and continue to be important to this process. This review will focus in on work by ourselves and others that have used murine models assessing the effects in vivo of the Friend virus complex (FVC, composed of a spleen focus forming virus and a murine leukemia helper virus) and solid tumors with metastatic potential in order to evaluate new and innovative therapies. These therapies include radiation, hyperthermia, and newly recognized naturally occurring biomolecules termed cytokines. These cytokines include, but are not limited to, the interferons, the tumor necrosis factors, the interleukins, the hematopoietic colony stimulating factors, lactoferrin and E-type prostaglandins. For example, it has been found that lactoferrin, when administered early enough, prolongs the survival of mice injected, but not yet infected, with the FVC. Of even greater potential usefulness is that mice already infected with the FVC can be completely rescued from death by treatment with split low dosage (150 cGy) total body irradiation. Irradiation treatment was associated with restoration of the T helper to T suppressor cell ratio, natural killer cell activity and marrow proliferative responses to the mitogens PHA and con A which were compromised by the FVC. More recent studies in our laboratory have demonstrated the potential of the interleukins and colony stimulating factors to decrease the metastatic potential of the B16 melanoma and the Lewis Lung Carcinoma cell lines. The cytokines can act in greater than additive fashion and combinations of therapies are possible. This review is meant to increase the awareness of these investigative animal models and the new types of combination therapies that can then be used as the basis for future clinical trials evaluating therapeutic efficacy.
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PMID:New therapeutic strategies in the treatment of murine diseases induced by virus and solid tumors: biology and implications for the potential treatment of human leukemia, AIDS, and solid tumors. 225 87

There is evidence for defective DNA repair in xeroderma pigmentosum, Cockayne's syndrome, and trichothiodystrophy, but for increased cancer risk only in xeroderma pigmentosum. Natural and adaptive immune surveillance and mutant frequency to 6-thioguanine resistance in circulating T-lymphocytes were studied in five patients with xeroderma pigmentosum, two with Cockayne's syndrome, and one with trichothiodystrophy. Forty-eight-hour cutaneous hypersensitivity responses to recall antigens excluded anergy and circulating CD3+, CD4+, CD8+, and CD16+ cell numbers were within normal limits in all patients tested, as were proliferative lymphocyte responses to PHA, except in the trichothiodystrophy patient. Proliferative responses to recall antigens (PPD, SKSD, and Candida) showed that all patients responded to one or more antigens. Direct natural killer cytotoxicity measured against the human erythromyeloid leukaemia cell line K562 using a 4-h 51Cr release assay was significantly reduced in xeroderma pigmentosum (specific cytotoxicity less than mean +/- SD greater than 17.4 +/- 9.4 per cent, with effector:target cell ratio of 50:1) compared to normal controls (45.8 +/- 17.8), but normal in Cockayne's syndrome and trichothiodystrophy. Generation of lymphokine activated killer cell activity was normal in the two xeroderma pigmentosum lines tested. The mutant frequency in the xeroderma pigmentosum donors was significantly increased (p less than 0.01) and was elevated in the two Cockayne's syndrome donors, taking age into account. No mutants were observed from the single trichothiodystrophy donor. These findings suggest that reduced natural killer cell activity may contribute to the greatly increased susceptibility to skin cancer in xeroderma pigmentosum.
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PMID:Immune function, mutant frequency, and cancer risk in the DNA repair defective genodermatoses xeroderma pigmentosum, Cockayne's syndrome, and trichothiodystrophy. 238 95

In 1989, 65%-75% of previously untreated adults with ALL or AML may be expected to enter complete remission. Approximately 40% of these completely responding patients, whether they are treated with intensive chemotherapy, intensive chemotherapy followed by autologous bone marrow transplantation, or allogeneic bone marrow transplantation, remain disease-free after 3 years of follow-up. As such, the likelihood for cure for adults with acute leukemia is approximately 25%-30%. At the present time, no new chemotherapeutic agents of significant importance are on the horizon. Furthermore, it seems doubtful that the mere juggling of drug doses will have any measurable effect on treatment outcome. The use of hematopoietic growth factors, either to allow added tolerance of intensive therapy or to synchronize leukemic cells kinetically, is now under study. Perhaps the most promising area of present investigations deals with immune manipulation. The administration of immunotoxins (a drug or a cell poison chemically linked to a leukemia-related monoclonal antibody) has been associated with promising results in eradicating minimal residual disease in animal model systems. Similarly, attempts at harnessing the graft-versus-leukemia effect without the eligibility restrictions and toxicities associated with the allograft procedure, through the use of lymphokines as enhancers of natural killer cell activity, have also proven to be effective in pre-clinical trials. With the availability of hematopoietic growth factors, immunotoxins, and lymphokines, clinical research in acute leukemia in the future will no longer focus on cytotoxic drugs alone but rather on how the addition of biological agents can prolong the duration of complete remission and increase the potential for cure.
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PMID:Acute leukemias in adults: an overview of recent strategies. 231 10

The morphologic, immunologic, genotypic and functional properties of peripheral blood and bone marrow cells or cultured cells from four patients with a clinically aggressive non-T, non-B natural killer cell leukaemia/lymphoma (ANKL/L) are described. The leukaemic cells possessed medium to large granules in the cytoplasm, antigens against CD38, CD2, OKIa 1 and NKH-1 CD56) monoclonal antibodies on their cell-surface, and also showed natural killer (NK) activity. In addition, these ANKL/L belonged to neither T- nor B-cell lineage, proved by studying clonal gene rearrangement for the T beta, T gamma and T delta receptors, and immunoglobulin. After comparing them with the seven cases of ANKL/L reported in other institutions, with regard to immunophenotype, genotype and function, we conclude that ANKL/L originating from a third lineage of lymphoid cells is a distinct clinical entity.
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PMID:Aggressive natural killer cell leukaemia/lymphoma: report of four cases and review of the literature. Possible existence of a new clinical entity originating from the third lineage of lymphoid cells. 226 60

A new serine protease was encoded by a clone isolated from a murine cytotoxic T-lymphocyte complementary DNA library by an RNA-hybridization competition protocol. Complementary transcripts were detected in cytotoxic T lymphocytes, spleen cells from nude mice, a rat natural killer cell leukemia, and in two of eight T-helper clones (both cytotoxic), but not in normal mouse kidney, liver, spleen, or thymus, nor in several tested T- and B-cell tumors. T-cell activation with concanavalin A plus interleukin-2 induced spleen cells to express this gene with kinetics correlating with the acquisition of cytolytic capacity. The nucleotide sequence of this gene encoded an amino acid sequence of approximately 25,700 daltons, with 25 to 35 percent identity to members of the serine protease family. The active site "charge-relay" residues (His57, Asp102, and Ser195 of the chymotrypsin numbering system) are conserved, as well as the trypsin-specific Asp (position 189 in trypsin). A Southern blot analysis indicated that this gene is conserved in humans, mouse, and chicken. This serine protease may have a role in lymphocyte lysis and a "lytic cascade."
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PMID:Cloning of a cDNA for a T cell-specific serine protease from a cytotoxic T lymphocyte. 242 55

The action of leukoregulin, a dominant tumor inhibitory lymphokine in native nonfractionated lymphokine preparations, was studied at the target cell level to ascertain its role as a molecular mediator in natural killer lymphocyte cytotoxicity. Leukoregulin was isolated from lymphokines produced by phytohemagglutinin stimulated human peripheral blood mononuclear leukocytes. Thirty minute leukoregulin treatment increased the sensitivity of human K562 leukemia cells to natural killer cell cytotoxicity. Maximum target cell sensitization to natural killer cytotoxicity was achieved within two hours. Measurement of K562 cell surface conformation by narrow angle forward light scatter and plasma membrane permeability by fluorescein diacetate fluorochromasia with a FACS IV flow cytometer demonstrated leukoregulin specific bio-membrane changes as early as five minutes with a maximum being attained within two hours of target cell exposure to leukoregulin. Analysis of K562 cells during development of a natural killer cell cytotoxicity reaction showed identical flow cytometric cell surface membrane changes to those developing in K562 cells exposed to leukoregulin alone. These observations suggest that leukoregulin is an intrinsic element in natural killer cell cytotoxicity and that the modulation of natural killer cell cytotoxicity may result from the early alteration in target cell surface membrane integrity induced by leukoregulin.
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PMID:Flow cytometric evaluation of leukoregulin as an intrinsic molecular mediator of natural killer lymphocyte cytotoxicity. 244 52

There is evidence for an increased incidence of lymphoproliferative disorders in patients with rheumatoid arthritis (RA). We present the clinical features of 4 patients with RA and chronic lymphatic leukaemia (CLL) which, occurring in a population of 1505 RA patients, represents a significantly increased prevalence of CLL (p less than 0.05) compared to the general population. These patients had significantly lower natural killer cell activity than matched rheumatoid controls (p less than 0.05) or normal controls (p less than 0.01) and we discuss this as a possible mechanism of association.
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PMID:Rheumatoid arthritis and chronic lymphatic leukaemia. 259 Nov 28

The morphologic, immunologic, genotypic, and functional properties of peripheral blood and bone marrow cells or cultured cells from two patients with a clinically aggressive non T, non B natural killer cell lymphoma/leukemia (ANKL/L) were described. The leukemic cells possessed medium to large granules in the cytoplasm, antigens against CD 38, CD 2, OKIal, and NKH-1 (N 901) monoclonal antibodies on their cell-surface, and also showed a high natural killer (NK) activity. In addition, these ANKL/L belonged to neither T-nor B-cell lineage, proved by studying clonal gene rearrangement for the T beta and T gamma receptor, and immunoglobulin. After we compared and investigated them with 9 cases of ANKL/L reported in other institutions, concerning immunophenotype, genotype and function, we reached the conclusion that the existence of ANKL/L originating from the third lineage in lymphoid cells is an obvious fact, suggesting this new clinical entity. It is important that all patients who have this type of a clinical disorder be diagnosed that there is no effective form of therapy at present.
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PMID:[Aggressive natural killer cell leukemia/lymphoma--possible existence of a new clinical entity originating from the third lineage of lymphoid cells]. 266 62

A new monoclonal antibody (MAB), IA61gG2a, has been derived from Balb/c mice after immunization with T-cell chronic lymphocytic leukemia (T-CLL). This monoclonal antibody, 1A6 was tested on normal human peripheral blood cells, leukemia patients' cells and leukemia-lymphoma cell lines. The results demonstrated that this antibody reacts with normal human T and B cells, but not with erythrocytes, granulocytes or platelets. Further examinations showed 10/11 leukemic patient cell types were positive with 1A6. In contrast, many leukemia-lymphoma cell lines were negative (14/17), i.e. T and B leukemia lymphoma cell lines, non-T and non-B leukemia cell lines as examined by complement mediated cytotoxicity test and immunofluorescence test. Other prominent characteristics of 1A6 MAB have been demonstrated, which include inhibition of myeloid colony formation (CFU-C) and suppression of human natural killer cell cytotoxicity (NKCC). These results suggest that 1A6 is a common marker for normal T, B, NK cells and leukemic patients cells having T and B cell origin, but 1A6 antigen is not expressed on many leukemia lymphoma cell lines. Therefore, it could be useful for studying malignant transformation of lymphoid cells.
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PMID:A monoclonal antibody 1A6 to T-cell recognizes a common antigen expressed on lymphocytes from normal and leukemic patients, and inhibits NK cell activity. 278 80


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