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 leukaemia-associated cell surface antigen p24/BA-2 is a single polypeptide chain with a molecular weight of 24,000. Treatment with glycosidases or exposure of cells to tunicamycin failed to show any change in the molecular weight of the antigen when examined by SDS-polyacrylamide gel electrophoresis. In addition, it failed to bind to lectin affinity columns of concanavalin A, lentil lectin or ricinus communis lectin. This is consistent with the absence of N-asparagine linked oligosaccharide chains on the antigen. Pulse-chase labelling of protein p24 shows a post-translational modification resulting in a molecular weight increase of approx. 500-1000. Alkaline treatment resulted in a decrease in molecular weight of approximately the same amount, suggesting that p24 contain some O-glycosidically linked oligosaccharide. Protein p24 has a basic pI of 7.3 which is unchanged after neuraminidase treatment. Protein P24/Ba-2 cannot be labelled by either the lipophilic photoactivatable nitrene reagent, hexanoyldiiodo-N-(4-azido-2-nitrophenyl)tyramine, or with [32P]phosphate. This suggests that the molecule is non-integral in nature and that it does not form an intimate association with the lipid matrix. Identical molecular weights, when reduced and non-reduced antigens were compared, suggest that it contains no internal disulphide linkages and failure to detect any other band on gradient gel SDS-polyacrylamide gel electrophoresis from 5-15% suggests that is is not strongly associated with any other structure.
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PMID:Biochemical characterisation of leukaemia-associated antigen p24 defined by the monoclonal antibody BA-2. 695 Jul 91

A concentrated live retrovirus is required for in vitro experiments. A cuprammonium-regenerated cellulose hollow fiber, termed BMM, originally developed for biohazardous viral removal, was used to concentrate two different retroviruses, an ecotropic murine leukemia virus (MuLV) and human immunodeficiency virus (HIV). The BMM was useful for concentrating live virus suspension 10- to 30-fold from 500-1000 ml of culture supernatant. The ecotropic MuLV concentrated by BMM was demonstrated to be viable and biologically intact by XC plaque-forming assay and reverse transcriptase assay. The concentrated MuLV reached a much higher titer in the spleen in mice than the original one. The virus concentration assessed by p24 antigen for HIV was clearly higher than that of the original culture supernatant of HIV-infected cell lines. Since BMM hollow fibers trapped viruses by the sieving mechanism but not by adsorption, the viral particles were recovered by washing and the total live virus recovery rate was high, about 50%. Furthermore 60 min sufficed to handle 1000 ml of supernatant in the case of a filtration area of 0.03 m2. These results show that the BMM provides us with a rapid, safe and efficient method for concentrating live retroviruses.
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PMID:Concentration of live retrovirus with a regenerated cellulose hollow fiber, BMM. 752 92

Human peripheral blood lymphocytes (PBLs) were transduced with a number of recombinant retroviruses including RRz2, an LNL6-based virus with a ribozyme targeted to the human immunodeficiency virus (HIV) tat gene transcript inserted within the 3' region of the neomycin-resistance gene; RASH5, and LNHL-based virus containing an antisense sequence to the 5' leader region of HIV-1 downstream of the human cytomegalovirus promoter; and R20TAR, an LXSN-based virus with 20 tandem copies of the HIV-1 trans-activation response element sequence driven by the Moloney murine leukemia virus long terminal repeat. After G418 selection, transduced PBLs were challenged with the HIV-1 laboratory strain IIIB and a primary clinical isolate of HIV-1, 82H. Results showed that PBLs from different donors could be transduced and that this conferred resistance to HIV-1 infection. For each of the constructs, a reduction of approximately 70% in p24 antigen level relative to the corresponding control-vector-transduced PBLs was observed. Molecular analyses showed constitutive expression of all the transduced genes from the retroviral long terminal repeat, but no detectable transcript was seen from the internal human cytomegalovirus transcript was seen from the internal human cytomegalovirus promoter for the antisense construct. Transduction of, and consequent transgene expression in, PBLs did not impact on the surface expression of either CD4+/CD8+ (measured by flow cytometry) or on cell doubling time (examined by [3H]thymidine uptake). These results indicate the potential utility of these anti-HIV-1 gene therapeutic agents and show the preclinical value of this PBL assay system.
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PMID:Resistance to human immunodeficiency virus type 1 infection conferred by transduction of human peripheral blood lymphocytes with ribozyme, antisense, or polymeric trans-activation response element constructs. 763 80

Temperature elevation constitutes a beneficial component of the host defence against viral pathogens. However, heat treatment may be detrimental to HTLV-I-infected cells by increasing virion and oncoprotein production. We investigated the effects of thermal elevation on the in vitro replication of HTLV-I (human T-cell leukaemia/lymphoma virus type I) in MT-2 cells, an HTLV-I-transformed lymphoid cell line. We found that HTLV-I replication in MT-2 cells was markedly increased as demonstrated by a nearly 2-fold increase in detection of viral p24 antigen and a 20-fold increase in reverse transcriptase activity during up to 5 h of heat treatment at 42 degrees C. The results suggest that physiologic thermal elevations may induce viral production in HTLV-I-infected individuals.
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PMID:In vitro thermal enhancement of human T-cell leukaemia/lymphoma virus type I (HTLV-I) in HTLV-I-transformed cells. 768 46

We have investigated the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and several potent vitamin D3 analogs [1,25(OH)2-16-ene-23-yne-D3; 1,25(OH)2-16-ene-23-yne-26,27-F6-D3] on productive infection by human immunodeficiency virus (HIV) in human macrophages. Macrophages derived from the peripheral blood were either pretreated with the vitamin D3 analogs, washed, and exposed to HIV (pre-infection treatment) or were infected with HIV, washed, and cultured with the vitamin D3 compounds (post-infection treatment). After three days of HIV-infection, levels of p24 antigen were measured. Pretreatment of macrophages with either 1,25(OH)2D3 or 1,25(OH)2-16-ene-23-yne-26,27-F6-D3 (pre-infection treatment) increased productive HIV infection about 3.5-fold; 1,25(OH)2-16-ene-23-yne-D3 increased levels about 4.7-fold. In contrast, exposure of HIV infected macrophages to the vitamin D3 compounds (post-infection treatment) did not affect levels of HIV production compared to untreated controls. Soluble CD4 completely inhibited productive HIV infection of macrophages pretreated with vitamin D3 analogs. Also, the vitamin D3 compounds slightly decreased CD4 expression on macrophages. The mechanism of enhanced productive HIV infection by the vitamin D3 compounds is unclear, but can not be explained by either alteration of CD4 expression or entry into cells by a CD4-independent route. These studies may have implications for both the basic biology of HIV infectious production and possibly clinical treatment of AIDS patients.
Leukemia 1993 Oct
PMID:Effect of 1,25-dihydroxyvitamin D3 and its analogs on human immunodeficiency virus infection in monocytes/macrophages. 769 90

We have examined the effects of antisense oligomers (AOs) of various lengths, sequences and chemistry on the proliferation of eight different cell lines, five derived from patients with chronic myelogenous leukemia (CML) and three from other sources. In general, phosphodiester AOs were inactive, presumably due to degradation by nucleases present in fetal calf serum. Both BA2 and B3A2 phosphorothiolate AOs (but not corresponding sense oligomers) significantly inhibited the proliferation of three CML cell lines (BV173, LAMA84, and KYO1), but the effect was independent of the type of breakpoint expressed by each cell line, suggesting that the inhibition was sequence dependent but not sequence specific. The CML cell lines tested showed different sensitivities to inhibition of proliferation by AOs--lines with defective expression of the normal ABL protooncogene (e.g. BV173) were more readily inhibited than lines with a normal ABL message (e.g. K562). We conclude that further studies are necessary to delineate the precise mechanism(s) by which CML cell proliferation is inhibited by AOs.
Leukemia 1994 Dec
PMID:Antisense BCR-ABL oligomers cause non-specific inhibition of chronic myeloid leukemia cell lines. 780 4

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
Leukemia 1994
PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21

The antiretroviral activity of two new lipophilic derivatives of azidothymidine (AZT), N4-hexadecyl-2'-deoxyribocytidylyl-(3',5')-3'-azido-2',3'-deoxythy midine (N4-hexadecyldC-AZT) and N4-palmitoyl-2'-deoxyribocytidylyl-(3',5')-3'-azido-2',3'-deoxythy midine (N4-palmitoyldC-AZT) was evaluated in comparison to AZT. In vitro the drugs were tested in human immunodeficiency virus 1 (HIV-1) infected CD4+ HeLa and H9 cells. The in vivo antiviral effect of these derivatives was analysed in Rauscher leukemia virus (RLV) infected mice. The derivatives were incorporated into small liposomes. In vitro both derivatives inhibited virus proliferation in both HIV-1 infected cell lines in a similar dose-responsive manner as AZT. In a plaque reduction assay, using HeLa cells, the IC50 values were 0.035 microM for AZT, 0.5 microM for N4-hexadecyldC-AZT and 4.5 microM for N4-palmitoyldC-AZT, whereas p24 antigen analysis on H9 cells gave IC50 values of 0.005 microM, 0.05 microM and 0.05 microM, respectively. RLV infected mice were treated with intermittent schedules i.p. or i.v. on days 1, 6, 11, and days 16 or 0, 3, 7, and 11 after infection. Regimens with further delayed drug application were on days 3, 7, and 11 and 7 and 11 only. While i.p. treatment with total doses of 380-1140 mg/kg free AZT resulted in 10-30% inhibition of RLV induced splenomegaly, the derivatives gave inhibitions of 37-94%. Late onset of treatment with the derivatives was significantly more effective as compared to free AZT. Intravenous treatment with N4-hexadecyldC-AZT was effective, but with AZT was inactive. The discrepancy in antiviral activity of the AZT derivatives found between the in vitro and in vivo test systems emphasizes the importance of investigating the activity of drug derivatives in vivo.
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PMID:New lipophilic alkyl/acyl dinucleoside phosphates as derivatives of 3'-azido-3'-deoxythymidine: inhibition of HIV-1 replication in vitro and antiviral activity against Rauscher leukemia virus infected mice with delayed treatment regimens. 794 15

A leukemia-associated CD9 glycoprotein antigen released into the extracellular milieu from acute lymphoblastic leukemia cells has been detected using a unique lectin-monoclonal antibody immunoassay. It has been demonstrated that the release of CD9 antigen is an active process and is associated with active cell growth. In addition, the difference of carbohydrate moiety, and hence glycosylation, in the CD9 antigen derived from lymphoblasts and neuroblasts was verified using lectin affinity chromatography. The lectin affinity of the carbohydrate moiety of lymphoblast CD9 antigen would indicate the presence of N-linked oligosaccharide chains having groups of N-acetyl glucosamine residues, a mannose core and a terminal D-galactose. The soluble CD9 antigen is specifically detected in plasma from ALL patients at the time of diagnosis, in cerebrospinal fluid from patients with central nervous system involvement, and spent medium from CD9-positive leukemic blasts obtained at the time of diagnosis. Interestingly when bone marrow cells taken from patients in complete remission were studied, a distinct amount of CD9 antigen was released into spent medium in some of the cases. All of these patients have subsequently developed hematological relapse. The present data suggest that shedding of CD9 antigen by leukemic cells may enable the clinical monitoring of residual leukemic cell burden.
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PMID:Shedding of CD9 antigen in acute lymphoblastic leukemia. 818 Jun

The phenotypic and biologic properties of malignant cells in a case of aggressive mastocytosis with multi-organ involvement, circulating mast cell precursors and absence of skin infiltrates were analyzed. Circulating mast cell precursors were detected by immunostaining using antibodies against mast cell tryptase as well as by electron microscopy. These progenitors were tryptase+/chymase- (MCT) and accounted for 10 to 20% of nucleated mononuclear blood cells (MNC). A subset of them contained metachromatic granules. As assessed by combined toluidine blue/immunofluorescence staining, the granulated mast cell precursors were found to express CD9 (P24), CD33 (gp67) and CD44 (Pgp-1), but not basophil-related markers (CD11b (C3biR), CDw17 (lactosylceramide), CD123 (il-3R alpha))or monocyte-related antigens (CD14, CD15). Expression of the mast cell growth factor (MGF) receptor, c-kit(CD117), was also demonstrable, whereas the skin mast cell marker C5aR (CD88) could not be detected on mast cell precursors. The ligand of c-kit, recombinant human (rh) stem cell factor (SCF = MGF), induced histamine release from circulating mast cell progenitors, whereas rhC5a, a potent skin mast cell-/basophil-agonist, was ineffective over the dose-range (10(-9) to 10(-7(M)) tested. Analysis of mast cell antigens in malignant mastocytosis or mast cell leukemias may be helpful to establish a diagnosis and to determine the phenotype of the clone.
Leukemia 1996 Jan
PMID:A case of malignant mastocytosis with circulating mast cell precursors: biologic and phenotypic characterization of the malignant clone. 855 22


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