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)

Relapse after marrow transplantation occurs despite total body irradiation and high doses of chemotherapy used to prepare the recipient. Recurrence rate is particularly high after autologous transplantation. In order to eliminate minimal residual disease persistent after marrow grafting, immunotherapy is currently being explored as a treatment modality that is non-cross-reactive with radiation and chemotherapy. This review describes first clinical results on the use of interferons and interleukin-2 in marrow transplant recipients as well as attempts to induce graft-versus-leukemia effects.
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PMID:Trying to overcome residual disease after bone marrow transplantation for hematologic malignancies. 128 96

The peripheral nervous system is frequently impaired in patients who have cancer. This impairment often results from toxicity of treatment but may also be due to direct invasion by tumor or may be part of a paraneoplastic syndrome. This review summarizes the recent literature regarding peripheral neuropathies and myopathies that are seen in patients with cancer. Highlights include the neuromuscular toxicity of some of the newer chemotherapeutic agents and immune mediators such as taxol and interleukin-2; a discussion of some of the agents being investigated for chemoprotection and rescue; an assessment of the evidence supporting the concept of motor neuron disease as a paraneoplastic disorder; and an interesting case report of megakaryoblastic leukemia invading peripheral nerves. Also summarized are some nice reviews and prospective studies of the toxicity of more conventional treatments.
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PMID:Neuromuscular toxicity of therapy. 132 35

Interleukin-2 (IL-2) promotes the generation and proliferation of killer cells in the peripheral blood and bone marrow (BM) both in vitro and in vivo. When employed in a syngeneic bone marrow transplantation (BMT) setting and followed by IL-2 therapy, murine BM cells activated with IL-2 in vitro (ABM) demonstrate potent graft-versus-leukemia (GVL) and anticytomegalovirus effects. ABM cells retain the capacity to reconstitute the hemopoietic system both in normal and leukemic mice. This therapy does not cause graft-versus-host disease (GVHD). Human ABM cells carry out purging of leukemia without loss of progenitor cell activity in vitro. The purging ability of ABM can be augmented by interleukin-1, interferon, and tumor necrosis factor. IL-2 therapy stimulates the veto suppressor cell activity of T cell-depleted BM, and has reduced GVHD and permitted engraftment of mismatched allogeneic BM in murine models. Future studies should determine the optimum treatment schedules with IL-2 for improving the GVL effect in autologous BMT, and for abolishing GVHD in allogeneic BMT settings.
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PMID:Interleukin-2 in bone marrow transplantation: preclinical studies. 132 64

An African lioness from the Zoo of Zurich had to be euthanized because of an inoperable tumor. The serum tested negative for feline leukemia virus (FeLV) p27 antigen by enzyme-linked immunosorbent assay (ELISA) but was strongly positive for feline immunodeficiency virus (FIV) antibodies by ELISA and Western blot. When her only offspring and mate were tested for FIV, high antibody titers to FIV were also found in their serum. Lymphocytes were prepared from these two lions on different occasions and co-cultivated with specific pathogen free (SPF) cat lymphocytes in the presence of concanavalin A and recombinant human interleukin-2 (IL-2) for 6 weeks. The cell culture supernatants tested negative for Mg(2+)-dependent reverse transcriptase and FIV p24 by a double antibody sandwich ELISA throughout the culture period. Whole blood and buffy coat cells collected from these two lions were transmitted by intraperitoneal injection into two SPF cats. The two cats did not seroconvert for a period of 11 months nor could reverse transcriptase activity and FIV p24 antigen be demonstrated in the supernatant of several lymphocyte cultures. To determine the importance of lentivirus infections in zoo-kept wild felids, 124 serum samples were obtained from African lions, Indian and Siberian tigers, snow leopards, panthers, cheetahs and other wild cats from nine European zoos. In addition, serum samples collected from 12 Asiatic lions originating from Gir forest in the Indian State of Gujarat were included in this study. The sera were tested for antibodies to FIV, FeLV and feline syncytium-forming virus (FeSFV) by ELISA and Western blot using the respective viruses after gradient purification. In addition, some of the sera were also tested for antibodies to equine infectious anemia virus (EIAV) and Visna-Maedi virus (VMV). Antibodies to FIV were found in 30/53 (57%) of African lions, one of 18 tigers and one of four panthers. All other sera including those collected from the 12 Asiatic lions were negative for FIV antibodies. Some of the FIV positive lion sera had high antibody titers producing strong bands on Western blot strips even in dilutions of >> 1:1000. The Western blot pattern of the lion sera differed from that of domestic cats in that primarily p24 and to a lesser degree p17 was recognized. Antibodies to FeSFV were found in 14 animals (seven with strong, seven with intermediate, reaction). No correlation was found between FIV and FeSFV infection. Antibodies to FeLV were found in two cheetahs which later turned out to have been vaccinated with Leukocell, a FeLV vaccine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Retrovirus infections in non-domestic felids: serological studies and attempts to isolate a lentivirus. 133 98

Although the key role of human homeobox (HOX) genes in development is well established, their function in adult cells is still under scrutiny. We have analyzed, in normal adult blood cell subpopulations, acute lymphoid leukemia (ALL) cells lines, and primary blasts, the RNA expression of all HOX-2 cluster genes (5'-2.5, 2.4, 2.3, 2.2, 2.1, 2.6, 2.7, 2.8, 2.9, 3') and nine genes in the HOX-1, -3, and -4 cluster by Northern blotting, RNAse protection, and/or reverse transcriptase polymerase chain reaction (RT-PCR). The analyzed HOX-1, -3, and -4 genes were never expressed in all tested cell populations. Natural killer (NK) cells activated in interleukin-2 (IL-2)/IL-1 beta-treated cultures exhibit a gradually increasing, abundant expression of three HOX-2 genes (2.2, 2.6, 2.8), while three other genes (2.3, 2.1, 2.7) are expressed at a lower level at late culture times. However, no HOX-2 gene is expressed in quiescent lymphocytes (NK, B and T [T-cell receptor (TCR) alpha/beta, gamma/delta lymphocytes, thymocytes] cells), granulocytes, and monocytes. In B- and T-ALL cell lines, HOX-2 genes are expressed according to different patterns: (1) widespread transcription (seven of nine genes, including 2.3 and 2.6) in the Peer line bearing the TCR gamma/delta; (2) expression of 2.5, 2.2, and 2.6 in the SEZ 627 line, which derives from an HTLV-1+ T-helper leukemia; (3) transcription of 2.3 and 2.6 in both the T-ALL CEM line and four B-ALL lines (interestingly, CALLA- B-ALL lines are constantly 2.3/2.6 RNA+); (4) no HOX-2 gene expression was detected in one T- and two B-ALL lines. Primary blasts from five T- and five pre-B-ALL showed selective expression of one or more HOX-2 genes, namely 2.5, 2.2, 2.6, and 2.7. Our data are compatible with the hypothesis that selected HOX-2 genes play a role in the IL-2/IL-1 beta-induced activation and/or proliferation of normal NK lymphocytes and possibly in the oncogenetic process of some T- and B-ALL.
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PMID:Expression of selected human HOX-2 genes in B/T acute lymphoid leukemia and interleukin-2/interleukin-1 beta-stimulated natural killer lymphocytes. 135 62

While recent studies in Rhesus monkeys have pointed out the importance of an intact nef gene for the development of acquired immunodeficiency syndrome (AIDS), no biological function has been so far unambiguously attributed to its product. Since Nef has been described to possess GTP-binding properties and to down-regulate CD4 cell surface expression, we looked for evidences of Nef interfering with the transduction of activating signals in human CD4+ T cells. We used a murine leukemia retroviral vector to express the HIV-1BRU nef gene in two permanent tumoral T-cell lines (CEM and Jurkat) and in two nonimmortalized, interleukin-2 (IL2)-dependent, T-cell clones. The single copy recombinant provirus integrated in the genome of these cells directed the synthesis of a 27-kD protein with a half-life greater than 5 h. The levels of expression of cell surface molecules involved in T-cell functions (CD4, CD3, CD28, CD29, IL-2 receptor) were not modified in cell populations expressing Nef. In immunocompetent T-cell clones, cell proliferation and lymphokine production in response to activating stimuli (IL-2, alloantigens, phorbol esters, or antibodies directed against CD2, CD3, CD4, CD28) remained unmodified. Moreover, the presence of Nef did not change the kinetics of human immunodeficiency virus (HIV) infection.
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PMID:Activation pathways and human immunodeficiency virus type 1 replication are not altered in CD4+ T cells expressing the nef protein. 135 46

Soluble Interleukin-2 Receptor (sIl-2R) and Tumor Necrosis Factor-alpha (TNF-alpha) have been found significantly increased in serum samples of patients with HCL at diagnosis and a strict correlation with leukemic burden has been reported. Furthermore, following therapy, serological monitoring of these cytokines may be considered a useful tool for controlling therapeutic efficacy and for detection of minimal residual disease. Eighteen HCL patients, treated with 2-Chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily for 7 days, entered the study all of them showing increased levels of sIL-2R and TNF-alpha prior to therapy. After therapy, serum levels were reassessed and a remarkable decrease was recorded in all cases. In particular, after 1 month by the end of treatment sIL-2R and TNF-alpha decreased from 3,377 +/- 2,303 to 149 +/- 96 pM/ml (p = 0.00003) and from 38 +/- 41 to 18 +/- 18 pg/ml (p = 0.015) respectively. The only 3 patients who did not normalize sIL-2R and TNF-alpha levels showed also an evident persistence of the disease in the marrow. In conclusion, 2-CdA leads to a rapid normalization of the increased levels of sIL-2R and TNF-alpha in the majority of HCL patients. Furthermore, monitoring of these cytokines represents a useful tool for detecting minimal residual disease.
Leukemia 1992 Nov
PMID:Biological markers and minimal residual disease in hairy cell leukemia. 135 4

A significant elevation in the percentage of CD4+ and CD8+ T-lymphocytes expressing major histocompatibility complex (MHC) Class II antigens was observed in the blood of cats shortly after they were experimentally infected with feline immunodeficiency virus (FIV). In addition to an increase in the relative proportion of T-lymphocytes expressing Class II antigens, there was an increase in the density of Class II antigens on the cell surface. These elevations were still evident at the completion of the 5 month study. A second group of cats that had been infected with FIV for almost 5 years, and with either normal or abnormally low levels of CD4+ T-lymphocytes, had similar elevations in MHC II expression, suggesting that such abnormalities are lifelong. Cats with chronic (2 year) feline leukemia virus (FeLV) infection or dual FIV/FeLV infections also showed similar alterations in MHC II expression on CD4+ and CD8+ T-lymphocytes, suggesting that these alterations were not FIV specific. Feline T-lymphocytes expressed more MHC II antigen and interleukin-2 (IL-2) receptor following stimulation in vitro with conconavalin A and IL-2, demonstrating that feline T-lymphocytes respond to activation signals in a manner similar to T-lymphocytes of other species. However, changes in MHC II expression on T-cells of FIV infected cats were not explainable by viral induced T-cell activation alone, because FIV infected cats with elevated MHC II expression did not have coincident elevations in IL-2 receptor expression.
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PMID:Persistent upregulation of MHC class II antigen expression on T-lymphocytes from cats experimentally infected with feline immunodeficiency virus. 136 10

Results concerning a possible link between susceptibility to natural-cell-mediated immune cytolysis and the multi-drug resistance (MDR) phenotype are conflicting. We evaluated in human acute lymphocytic leukemia the relationship between acquired drug resistance and susceptibility to cytolysis mediated by endogenous, interferon-activated, and interleukin-2-activated natural cytotoxic cells. Eight human leukemia drug-resistant/sensitive cell line pairs were evaluated; drug-resistant sub-lines included those selected for primary resistance to adriamycin, etoposide, teniposide, vincristine, and vinblastine. A majority of P-glycoprotein-positive MDR sub-lines displayed slight but statistically significant resistance to endogenous and/or interferon-activated natural-killer(NK)-cell-mediated lysis, as compared with the drug-sensitive parental type. P-glycoprotein-negative sub-lines displayed variable NK susceptibility; within this group, the variants selected for primary etoposide resistance were more susceptible to NK cytolysis than parental cells. Results of cold-target-inhibition experiments suggest that altered NK susceptibility does not arise solely from modulation of NK target recognition and adherence structures. IL2-activated killer (LAK) cells lysed both drug-sensitive and drug-resistant lines. Two MDR lines selected for primary etoposide resistance displayed enhanced LAK susceptibility. In contrast, the 2 variants selected for resistance to adriamycin exhibited partial resistance to LAK-mediated killing, which could be overcome at high effector-to-target ratios. Our results support the development of interleukin-2/LAK immunotherapy for the treatment of leukemias with acquired drug resistance.
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PMID:The relationship between multi-drug resistance and resistance to natural-killer-cell and lymphokine-activated killer-cell lysis in human leukemic cell lines. 137 Apr 37

Monoclonal antibodies (MAbs) raised against human T-cell lymphotropic virus type I (HTLV-I) recognized five distinct antigenic domains of viral env gene-encoded proteins. By using recombinant env proteins and synthetic peptides as mapping antigens, it was determined that the most immunogenic region represented a central portion of the retroviral surface protein (domain 2; amino acids 165 to 191). However, only a single MAb was able to react strongly with native viral proteins. This antibody (clone 6C2) was directed to an epitope within domain 4 (amino acids 210 to 306) of the retroviral env gene and reacted with envelope proteins in both HTLV-I and HTLV-II, as determined by immunoprecipitation, solid-phase binding, and immunoblotting. No reactivity against envelope components of other human retroviruses, including human immunodeficiency virus types 1 and 2, was present. Flow cytometry data demonstrated that MAb 6C2 reacted with cell lines chronically infected with HTLV-I or HTLV-II and also with surface antigens expressed on fresh adult T-cell leukemia cells, following up-regulation with interleukin-2. By a chemiluminescence immunoassay procedure, picogram amounts of viral surface protein could be detected in the unconcentrated supernatants of HTLV-infected cell lines and in diagnostic cultures. Levels of env and gag proteins released by cells into culture supernatants were not directly related to percent expression of cell surface viral-coat proteins. Further, the molar ratio of p19 to gp46 in conditioned media varied from strain to strain, possibly reflecting differences in viral assembly or packaging mechanisms. MAb 6C2 will be of value in characterizing the biochemical and immunological behavior of retroviral env gene proteins and in studying the interaction of HTLV-I and HTLV-II with their receptors.
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PMID:Monoclonal antibodies and chemiluminescence immunoassay for detection of the surface protein of human T-cell lymphotropic virus. 137 16


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