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

Human T-cell leukemia virus type I (HTLV-I) antibody detection has been widely used to screen HTLV-I carriers. Sometimes, however, it gives false positive or negative results. A demonstration of the HTLV-I provirus from patients' peripheral blood mononuclear cells (PBMC) should, therefore, give the crucial evidence for them being HTLV-I carriers. We established a simple and reliable method using the polymerase chain reaction (PCR) to detect one molecule of HTLV-I provirus in 100 x 10(3) PBMC, during which internal control primers for the human beta-globin gene were also employed in the same reaction tube to check the success of the amplification reaction. We can thus easily avoid any false negative judgement and quantitate the HTLV-I provirus in PBMC simply by diluting the sample before PCR. One ml blood was enough for ten or more determinations by PCR. Analysis of seropositive blood from donors demonstrated a wide range for the number of HTLV-I provirus in PBMC. The method could conveniently be used for quantitating HTLV-I proviruses and following up HTLV-I carriers to study the pathophysiology and mode of HTLV-I transmission.
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PMID:A simple and reliable method for the detection and quantitation of the human T-cell leukemia virus type-I provirus in peripheral blood mononuclear cells of seropositive blood donors. 128 97

An investigation of the correlation between the gamma----beta-globin switch and DNA methylation was carried out. The restriction patterns obtained with methylation-sensitive and -insensitive enzymes indicated hypomethylation in the promoter region of the gamma-globin genes in fetal liver DNA but high methylation of the same region in all other samples (except in the presence of an elevated erythroblast count or leukemia). All samples appeared to be partially hypomethylated at the 5' end of the delta-globin gene and hypomethylated at the 3' region of the beta-globin gene. Although consistent with a role for DNA methylation in globin gene regulation, the results also suggest that other factors besides methylation may be required for regulation of the level of expression, and switching of the globin genes.
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PMID:DNA methylation patterns of the gamma delta beta-globin genes in human fetal and adult erythroid tissues. 131 7

The retroviral gene transfer system is a powerful tool for somatic gene therapy. A retroviral stock with a high viral titer and lacking replication-competent virus (RCV) is desirable for this type of gene transfer. To fulfill these requirements, we made a new packaging cell line, designated ampli-GPE. To reduce the homology between proviral DNA in the packaging cell and retroviral vector, the gag-pol and env genes of Moloney murine leukemia virus were separated onto two different plasmids, pGP-KV and pENV-KV, respectively, in which the 5' long terminal repeat and the 3' long terminal repeat had been replaced by the mouse metallothionein I promoter or the human beta-globin gene containing the polyadenylation site as control units for the gag-pol and env genes. In addition, these plasmids contained 69% of the bovine papillomavirus gene for gene amplification to obtain production of virus at a high titer. NIH 3T3 clones containing approximately 20 to 50 copies of the gag-pol and env genes were selected and designated ampli-GPE. When ampli-GPE was transfected with the N2 vector or pZipNeoSV(DHFR) derived from pZipNeoSV(X)1, we established clones producing titers of 5 x 10(6) and 1 x 10(6) CFU/ml, respectively. There was no sign of RCV generation in any virus-producing cells from ampli-GPE. However, virus-producing cells derived from psi 2 cells transfected with N2 did generate RCV. Thus, we showed that ampli-GPE, possessing the minimum complement of proviral genes, has potential for the development of a gene transfer system.
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PMID:A new retrovirus packaging cell for gene transfer constructed from amplified long terminal repeat-free chimeric proviral genes. 131 79

The polymerase chain reaction (PCR) method was used to determine the presence and amount of human T lymphotropic virus type I (HTLV-I) proviral DNA in central nervous system (CNS) tissue obtained at autopsy from 6 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), 1 patient with adult T-cell leukemia (ATL) and CNS infiltration of leukemic cells, and 9 control subjects with other neurological disorders. HTLV-I pX and env but not pol DNA were detected in CNS tissue from 5 of 6 patients with HAM/TSP. The ATL samples were positive for pX, env, and pol DNA by PCR. None of the control samples was consistently positive for HTLV-I by PCR, but all showed positive bands on beta-globin PCR. Quantitative PCR combined with histological studies showed no correlation between HTLV-I proviral DNA amounts and extent of perivascular mononuclear cell infiltration in the HAM/TSP CNS. Also, the amounts of pX and probably env DNA were greater in the HAM/TSP samples than in the ATL sample, although the extent of mononuclear cell infiltration was far less in the HAM/TSP samples than in the ATL sample. Therefore, in addition to infiltrating mononuclear cells, constituent cells of the CNS may harbor the HTLV-I genome, at least in the pX and env regions, in patients with HAM/TSP.
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PMID:Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I-associated myelopathy. 154 49

In Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL), some cytogenetic studies have suggested clonal derivation from a multipotential stem cell. The role of the product of the chimeric gene, P190, is not, however, well understood. We examined the expression of P190-type bcr/abl in single hematopoietic colonies obtained at various clinical stages of a patient with Ph1-positive ALL, using the polymerase chain reaction (PCR). Seven out of 58 colonies examined expressed P190-type bcr/abl. Five out of seven colonies were granulocyte/macrophage (GM) colonies and two were erythroid colonies. The cell lineages of these colonies were confirmed by testing for the expressions of the myeloperoxidase (MPO) gene in the GM colonies and the beta-globin gene in the erythroid colonies. These results suggest transformation of multipotential stem cell in this patient and confirm that expression of the P190-type bcr/abl fusion gene permits stem cell differentiation leading to Ph1-positive ALL.
Leukemia 1992 Aug
PMID:P190-type bcr/abl expressed in myeloid colonies in a patient with Ph1-positive acute lymphoblastic leukemia. 164 Jul 30

The transforming potential of the c-myc gene is shown here, for the first time, to include murine erythroid cells. Continuously growing cell lines were reproducibly generated by infection of day 13 CBA fetal liver cells with novel recombinant c-myc retroviruses. By cytostaining, most cells resembled early erythroblasts, but certain lines also contained significant numbers of hemoglobinized cells. RNA analysis revealed substantial expression of the genes encoding beta-globin and the erythroid-specific transcription factor GF-1. Although apparently immortal, the lines were not initially transplantable. Thus, constitutive myc expression in early erythroid cells can enhance their self-renewal capacity but is insufficient to fully transform them. The cell lines proliferated without the addition of exogenous factors, but their clonogenicity in semisolid medium was enhanced in the presence of erythropoietin, interleukin 3, and/or leukemia-inhibitory factor. In combination with either interleukin 3 or erythropoietin, leukemia-inhibitory factor also facilitated differentiation of certain lines. These results suggest that leukemia-inhibitory factor may have a previously unsuspected role in the regulation of erythropoiesis and could be considered as a possible therapeutic agent for the clinical management of erythroleukemia.
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PMID:Murine erythroid cell lines derived with c-myc retroviruses respond to leukemia-inhibitory factor, erythropoietin, and interleukin 3. 190 66

Peripheral blood blasts from a patient with acute megakaryoblastic leukemia were placed into liquid cultures with recombinant growth factors. Growth, but not differentiation, was supported by interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) for the first 30 days of culture. Sustained growth occurred only with GM-CSF and gave rise to the cell line MB-02, which has been in continuous culture for over 1 year. The cell line retained the surface phenotype of the leukemic megakaryoblasts except for the loss of glycoproteins Ib and IIb/IIIa, which were induced after exposure to phorbol esters. The induction of erythropoiesis occurred when GM-CSF-deprived cells were cultured with erythropoietin (Epo). Well-defined morphologic stages of differentiation ranging from primitive erythroblasts to nuclei-extruding normoblasts were seen. Transforming growth factor-beta inhibited GM-CSF- and Epo-dependent growth, but not erythroid maturation. Indirect immunofluorescence using globin chain-specific monoclonal antibodies detected fetal, but not adult hemoglobin in the uninduced cells. beta-globin was induced and gamma-globin was increased after Epo exposure. Both globin species accumulated in the developing erythrocytes until terminal differentiation. Quantitative S1 analysis of beta-like globin transcripts showed very low levels of epsilon- and beta-globin expression and high levels of gamma-globin expression in cells maintained in GM-CSF. Five days after induction with Epo, epsilon message decreased to barely detectable levels while gamma and beta transcripts increased threefold and 20-fold, respectively. This novel cell line not only retains many characteristics of the leukemic megakaryoblasts from which it was derived, but also can be induced to recapitulate apparent normal erythropoiesis.
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PMID:Granulocyte-macrophage colony-stimulating factor-dependent growth and erythropoietin-induced differentiation of a human cell line MB-02. 195 74

We have examined splice site activation in relation to intron structure in murine sarcoma virus (MuSV)-124 RNA. MuSV-124 contains inactive murine leukemia virus env gene splice sites (termed 5' env and 3' env) as well as cryptic sites in the gag and v-mos genes (termed 5' gag and 3' mos) which are activated for thermosensitive splicing by a 1,487-base intronic deletion in the MuSV-124 derived MuSVts110 retrovirus. To determine conditions permissive for splice site activation, we examined MuSV-124 mutants deleted in the 1,919-base intron bounded by the 5' gag and 3' mos sites. Several of these deletions activated thermosensitive splicing either at the same sites used in MuSVts110 or in a previously unreported temperature-sensitive splice event between the 5' gag and 3' env sites. These data suggested that the thermosensitive splicing phenotype characteristic of MuSVts110 required neither a specialized intron nor selection of a particular 3' splice site. The 3' env and 3' mos sites were found to compete for splicing to the 5' gag site; the more upstream 3' env site was exclusively used in MuSV-124 mutants containing both sites, whereas selection of the 3' mos site required removal of the 3' env site. Branchpoint sequences were found to have a potential regulatory role in thermosensitive splicing. Insertion of a beta-globin branchpoint sequence in a splicing-inactive MuSV-124 mutant activated efficient nonthermosensitive splicing at the 3' mos site, whereas a mutated branchpoint activated less efficient but thermosensitive splicing.
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PMID:Activation of cryptic splice sites in murine sarcoma virus-124 mutants. 217 Jun 71

Murine cell lines releasing helper-free recombinant retroviruses containing human alpha-globin and mouse/human hybrid beta-globin genes were generated. The expression of the hybrid beta-globin gene but not the human alpha-globin gene was regulated appropriately in infected mouse erythroid leukemia (MEL) cells. Murine bone marrow cells were infected by coculture with virus-producing cells and transplanted into lethally irradiated syngeneic recipients. Greater than 90% of the spleen colonies (12-15 days), which are derived from hemopoietic multipotential stem cells, showed proviral integration. Various levels of expression of the transduced globin genes were detected in all of the provirus-positive spleen colonies. Proviral sequences and transcripts from the transduced globin genes could also be detected in a few long-term reconstituted recipients in an observation period of 10 months after transplantation.
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PMID:Expression of human alpha-globin and mouse/human hybrid beta-globin genes in murine hemopoietic stem cells transduced by recombinant retroviruses. 234 42

Induction of globin gene expression in KMOE cells derived from a patient with acute erythremia was studied by Northern blot and S1 analysis. KMOE cells exposed to cytosine arabinofuranoside (Ara-C) synthesized beta-globin gene transcripts, however, in the presence of hemin gamma-globin gene transcripts. An increase in alpha-globin gene transcripts was also detectable in KMOE cells treated with both Ara-C and hemin. Upon exposure to hemin after exposure to Ara-C, or exposure to Ara-C after hemin, there was a 5-10-fold increase in gamma-globin gene transcripts compared to that of cells induced by hemin alone. Neither epsilon nor zeta globin transcripts were detected. The KMOE cell line, therefore, exhibits phenotypic properties of adult and fetal erythroid cells.
Leukemia 1987 Sep
PMID:Differential induction of adult and fetal globin gene expression in the human erythremia cell line KMOE. 244 37


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