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)

The therapeutic effects of fibroblast-mediated human interferon-alpha (IFN-alpha) gene therapy, alone or in combination with Doxorubicin (Dox), a chemotherapeutic agent, on the human leukemia-bearing nude mice were investigated. An NIH3T3 fibroblast clone (NIH3T3-IFN-alpha +) secreting the highest level of human IFN-alpha was obtained from the human IFN-alpha gene-transfected fibroblasts. Three days after i.p. Implantation of NIH3T3-IFN-alpha + cells, a certain level of human IFN-alpha could be detected in the sera from the implanted mice. After the NIH3T3-IFN-alpha + cells were implanted intraperitoneally into leukemia-bearing nude mice, the growth of leukemia was inhibited and the survival time of the leukemia-bearing mice was prolonged. The growth of leukemia was inhibited more obviously and the survival rate of the mice increased significantly when NIH3T3-IFN-alpha + cells were implanted in combination with Dox. These results demonstrate that fibroblast-mediated human IFN-alpha gene therapy is effective in treating leukemia and may achieve a better therapeutic effect when combined with Dox.
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PMID:Treatment of leukemia with fibroblast-mediated interferon-alpha gene therapy alone or in combination with doxorubicin. 868 76

The LH2 gene encodes a putative transcription factor containing two N-terminal LIM and one C-terminal HOX domains. The LH2 locus was mapped to 9q33-34.1, centromeric to the ABL gene. In a recent report, it was suggested that high levels of LH2 expression are consistently observed in chronic myeloid leukemia (CML) patients, whereas no transcription is detected in normal individuals. This led to the hypothesis that aberrant expression of LH2 may represent an additional mechanism for malignant cell proliferation in CML. We have studied the expression of LH2 in leucocytes from patients with CML or with other chronic myeloproliferative disorders (CMD), and from normal individuals, using an optimised reverse-transcription and polymerase chain reaction (PCR) technique. Twenty-seven out of 29 cDNA samples from normal individuals (93%), 49 out of 51 samples from CML patients (96%) and 20 out of 20 from Philadelphia chromosome-negative CMD showed evidence of LH2 expression. Similarly, LH2 transcription was also detected in leucocytes from CML patients in complete cytogenetic remission after treatment with interferon-alpha. Furthermore, all 36 EBV-induced lymphoblastoid cell lines established from six chronic phase CML patients showed unequivocal LH2 expression, regardless of the BCR-ABL status of the line (9 BCR-ABL positive, 27 BCR-ABL negative). We conclude that LH2 expression is not confined to CML cells, and that the t(9;22)(q34;qll) does not promote 'de novo' transcriptional activation of this gene.
Leukemia 1996 Jul
PMID:Expression of the LH2 gene in chronic myeloid leukaemia cells. 868 90

The cytogenetic evolution of 32 Philadelphia (Ph)-positive chronic myeloid leukemias (CML) receiving interferon-alpha (IFN-alpha) therapy was compared to the patterns in untreated CML and cases treated with busulfan (Bu), hydroxyurea (Hy), and allogeneic bone marrow transplantation (BMT). Half of the CML receiving IFN-alpha had at least one of the well-known major or minor route aberrations whereas 16 cases displayed unusual secondary abnormalities, of which only del(7p) and del(13q) were recurrent; a frequency significantly higher than in CML without therapy or after Bu and Hy treatment (P < 0.001) but similar to the one found post-BMT. The incidence of cases with cytogenetically divergent subclones, ie cell populations with unrelated aberrations in addition to the t(9;22), was also higher in the IFN-alpha group compared to the untreated, Bu and Hy groups (P < 0.01) but similar to the post-BMT group. Finally, 14 of the 32 IFN-alpha-treated CML displayed cytogenetic evolution already during the chronic phase; again a higher incidence than in the untreated, Bu and Hy groups (P < 0.001) but not different from the post-BMT group. These findings strongly indicate that IFN-alpha, directly or indirectly, can induce clones with aberrant chromosomal evolution patterns to evolve and proliferate, but the mechanisms underlying these cytogenetic peculiarities remain to be elucidated.
Leukemia 1996 Jul
PMID:Abberant cytogenetic evolution pattern of Philadelphia-positive chronic myeloid leukemia treated with interferon-alpha. 917 48

We have found that pretreatment of a human oral mucosal epithelial cell line KB with natural human interferon-alpha (IFN-alpha) augments the expression of intercellular adhesion molecule-1 (ICAM-1), and the complex of CD29 and CD49b, which is known as very late antigen (VLA)-2, in a dose-dependent manner, whereas the expression of other adhesion molecules such as CD44 leukocyte function associated antigen-3 (LFA-3), VLA-4 and endothelial leukocyte adhesion molecule-1 (ELAM-1) did not show any significant changes under the same conditions. The pretreatment of KB cells with IFN-alpha also induces the adhesion of these cells to the human leukemia T cell line MOLT-16 and to peripheral T lymphocytes in a dose-dependent manner. However, the adhesion of the above-mentioned T cells to KB cells was not inhibited by specific antibodies against ICAM-1, CD29, and CD49b. The results thus show that adhesion molecules other than ICAM-1, CD29, AND CD49b are responsible for the induced adhesion between T cells and IFN-alpha-pretreated KB cells.
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PMID:Natural human interferon-alpha enhances the expression of intracellular adhesion molecule-1, integrin alpha 2 and beta 1 by a mucosal epithelial cell line. 871 71

The present review has summarized the expression, production and effects of the human interleukins (IL) 1-11 and myelopoietic colony stimulating factors (CSF) in the established myeloid leukemia cell lines and in cells from patients with acute myeloid leukemia as well as the oncogene expression reported in these myeloid leukemia cell lines. The genetic dissection of leukemic myelopoiesis may provide new perspectives for the control of myeloid leukemias. Based on their expression of phenotypic markers (e.g., surface antigens, cytochemical staining, etc.), myeloid cell lines can be further subdivided into myelogenous, monocytic, erythroid and megakaryoblastic leukemia cell lines. Due to the close relationship of erythroid and megakaryoblastic progenitor cells and to the existence of a probably common precursor cell giving rise to these two different cell lineages, many megakaryoblastic cell lines express erythroid markers (e.g., expression of hemoglobin or glycophorin A) and conversely cell lines with a predominant erythroid profile might display megakaryoblastic features (e.g., platelets peroxidase or glycoproteins CD41, CD42b or CD61). The recent cloning of the specific cytokine: thrombopoietin (TPO) and its receptor generated a strong interest in these particular myeloid cell lines that are discussed in more detail in the present review. Both normal and leukemic megakaryocytopoiesis are stimulated by granulocyte-macrophage colony stimulating factor (GM-CSF), IL-3, GM-CSF/IL-3 fusion protein, IL-6, IL-11 and TPO but inhibited by IL-4, interferon-alpha (IFN-alpha) and IFN-gamma. Human megakaryoblastic leukemia cell lines have common biological features: high expression of the megakaryocytic specific antigen (CD41); high expression of early myeloid antigens (CD34, CD33 and CD13); constitutive expression of IL-6 and platelet-derived growth factor; a complex karyotype picture; expression of c-kit (the stem cell factor receptor); growth-dependency or -stimulation by IL-3 and/or GM-CSF; and in vivo tumorigenicity in mice associated with marked fibrosis. Whereas numerous chemical and biologic agents induce granulocytic and/or monocytic differentiation of myeloid leukemia cell lines, only a few agents including phorbol myristate acetate, vitamin D3, IFN-alpha, IL-6 and thrombin have been reported to induce megakaryocytic differentiation in the megakaryoblastic leukemia cells.
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PMID:Interleukins and colony stimulating factors in human myeloid leukemia cell lines. 875 Jun 18

A variant form of BCR/ABL junction was identified in a patient with chronic myelogenous leukaemia (CML). The BCR/ABL fusion mRNA of this patient showed in-frame junction between BCR exon c3 and ABL exon 2. Although the diagnosis of CML was made, the patient showed clinical features of essential thrombocythaemia (ET) rather than that of typical CML. Treatment with interferon-alpha showed no cytogenetic response. The c3-a2 type of BCR/ABL junction seems to be associated with elevated platelet count and thus could form a novel clinical entity different from typical CML.
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PMID:Elevated platelet count features the variant type of BCR/ABL junction in chronic myelogenous leukaemia. 875 98

We recently found that a human T-cell leukemia virus type 1-infected cell line, MT-2, could support the replication of hepatitis C virus (HCV) (N. Kato, T. Nakazawa, T. Mizutani, and K. Shimotohno, Biochem. Biophys. Res. Commun. 206:863-869, 1995). In order to develop a culture system in which HCV replicates more efficiently, we examined the efficiency of HCV replication in cloned MT-2 cell lines by the limiting dilution method. Consequently, we obtained five clones in which intracellular positive-stranded HCV RNA could be detected until at least 21 days postinoculation (p.i.), as opposed to 15 days p.i. in uncloned MT-2 cells. MT-2C, one of the five clones which supported HCV replication up to 30 days p.i., was used for further characterization of HCV replication. Semiquantitative analysis of HCV by PCR revealed that RNA synthesis in infected cells increased after inoculation, reached a maximum level at 4 days p.i., and maintained this level until at least 11 days p.i. The 5' untranslated region of negative-stranded HCV RNA was also detected in the infected cells by two different methods with strand specificity. These results suggest that HCV replicated and multiplied in the MT-2C cells. HCV-infected MT-2C cells that were treated with antibiotics, such as G418 and hygromycin B, sustained HCV RNA for a longer period than did untreated cells. We demonstrated inhibitory effects on HCV replication by an antisense oligonucleotide complementary to the HCV core encoding region and by interferon-alpha. Furthermore, cell-free viral transmission was demonstrated by this culture system. These results suggest that our cell culture system will be useful for studying the mechanism of HCV replication, for screening antiviral agents, and for developing HCV vaccines.
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PMID:Characterization of hepatitis C virus replication in cloned cells obtained from a human T-cell leukemia virus type 1-infected cell line, MT-2. 879 70

Previous experimental studies utilizing human recombinant interferon-alpha-2b (IFNalpha-2b) alone or with zidovudine (AZT) to treat established feline leukemia virus (FeLV) infection resulted in a significant reduction in circulating virus throughout a 49-day treatment period. However, the anti-FeLV effect of IFNalpha was limited by the production of IFNalpha-neutralizing antibodies detected 7 weeks after the start of treatment. AZT without IFNalpha had no effect on circulating virus load. To examine the hypothesis that combination chemoimmunotherapy might induce the clearance of FeLV infection, persistently infected cats were infused with activated lymphocytes, IFNalpha, and AZT 12 weeks after infection with FeLV. Recipient cats received weekly infusions of 1.46 x 10(8) lymphocytes activated in vitro with lectin/IL-2 comprised of 98% T cells and an even distribution of CD4+ and CD8+ lymphocytes. FeLV infection was cleared in 4 of 9 cats receiving combined therapy after four adoptive cell transfers. These cats remained negative for circulating virus during a 63-day treatment period (17 adoptive cell transfers) despite the production of anti-IFNalpha-neutralizing antibodies. Sequential development of virus-neutralizing and virus envelope antibody titers were detected in those cats which cleared retroviremia, an antiviral response that was absent in untreated control animals or nonresponders. Three of four responder cata remained negative for FeLV 95 days after treatment was discontinued. Treatment of cats with lymphocytes without chemotherapy failed to influence the course of FeLV infection. These results suggest that combined treatment using IFNalpha and adoptive lymphocyte transfer served to reconstitute antiviral humoral immunity, counteract immunosuppression, and induce the reversal of retroviremia.
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PMID:Reversal of feline leukemia virus infection by adoptive transfer of activated T lymphocytes, interferon alpha, and zidovudine. 882 Jun 1

A 57-year-old woman was diagnosed as having non-Hodgkin lymphoma (follicular mixed cell, B-cell type, Stage III) in February 1988. Since then, she had been treated with radiation and chemotherapy contained with alkylating agents and etoposide for 6 years. In April 1994, peripheral blood study disclosed leukocytosis with basophilia and thrombocytosis. Bone marrow was hypercellular. The karyotype of bone marrow cells was 46, XX, t(9:22) (q34:q11). Rearrangement of bcr was detected in bone marrow, but not in lymph node cells. On the basis of these findings, she was diagnosed as having the chronic phase of chronic myelogenous leukemia (CML) following the therapy for malignant lymphoma and treated with interferon-alpha (IFN-alpha) and hydroxycarbamide. Following this therapy, the lymphoadenopathy promptly disappeared and chromosome analysis showed disappearance of Ph chromosome positive cells. Although CML is rare in secondary leukemia, the present case seemed therapy-related CML and the treatment with IFN-alpha and hydroxycarbamide was effective for both CML and malignant lymphoma.
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PMID:[Successful treatment of combined interferon-alpha and hydroxycarbamide for chronic myelogenous leukemia following therapy for malignant lymphoma]. 891 75

We have selected an etoposide-resistant variant (CCRF-CEM/VP-16) of the human T-lymphoblastic CCRF-CEM leukemia for study. Resistance to the topoisomerase II (topo II) inhibitor was about 11-fold and stable. Other data revealed that the new cell line had acquired an atypical, non-P-glycoprotein overexpressing multidrug resistant (MDR) phenotype with cross-resistance to other topo II inhibitors (amsacrine, doxorubicin, and mitoxantrone) and to glucocorticoids, but not to novobiocin, ICRF-187, vincristine or cisplatin. In a first instance, we assumed that altered drug-topo II interactions, based on quantitative and/or qualitative modifications of the enzyme, are a cause of resistance in the cell line. We tried to modify the drug sensitivity of the cells by means of various agents and cytokines. Positive results were obtained with verapamil and, to a lesser extent, cyclosporin A, but they were not specific for the drug resistant variant and occurred in the parental CCRF-CEM as well. Other attempts with buthionine sulfoximine, novobiocin, pentoxifylline, interleukin-1, interferon-alpha, retinoic acid, TNF-alpha, bryostatin 1 or phorbol myristate acetate were substantially unsuccessful, thus confirming the difficulty of pharmacologically overcoming atypical MDR. More encouragingly, however, CCRF-CEM/VP-16 cells exhibited hypersensitivity to other agents, including actinomycin D and taxol.
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PMID:Development and partial characterization of a human T-lymphoblastic leukemic (CCRF-CEM) cell line resistant to etoposide. Analysis of possible circumventing approaches. 898 Nov 88


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