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)

Polymerase chain reaction amplification of reverse transcription products has demonstrated the presence of abl-bcr hybrid mRNAs in RNA from peripheral blood leucocytes of Philadelphia-chromosome-positive chronic myeloid leukaemia patients; such hybrid mRNAs can contain either of the alternative first exons of c-abl. A survey of 12 CMLs has shown that abl-bcr mRNAs occur in the leucocytes of some, but not all, patients, and that they are present both in chronic-phase and acute-phase leucocytes.
Leukemia 1993 May
PMID:ABL-BCR mRNAs transcribed from chromosome 9q+ in Philadelphia-chromosome-positive chronic myeloid leukaemia. 848 22

Polymerase chain reaction (PCR) was used to identify protein-tyrosine phosphatases (PTPases) in a human leukemic cell line, F-36P. Degenerate primers deduced from the highly conserved amino acid sequences in the catalytic domain of known PTPases were used for amplification. Among 16 clones sequenced, 13 were identical to known PTPases, whereas the other three clones were disclosed to encode novel PTPases. The expression pattern of one of the three newly identified PTPases, designated as F-36-12, was further analysed. In murine tissues, the F-36-12 message was predominantly expressed in brain, kidney, and intestine, and was weakly expressed in heart and thymus. In human hematopoietic cell lines, the F-36-12 message was preferentially expressed in a promyelocytic leukemic cell line, HL60, and two factor-dependent leukemic cell lines, F-36P and F-36E, that are dependent on granulocyte-macrophage colony-stimulating factor or interleukin-3 and erythropoietin, respectively. The transcript was approximately 8 kb long and the message level in HL60 cells was slightly increased at 24 hours and then slowly declined when treated with dimethyl sulfoxide for granulocyte differentiation, while the message level was rapidly decreased when treated with 12-O-tetradecanoylphorbol 13-acetate for monocyte/macrophage differentiation. These results show that several PTPases including three novel ones are expressed in a human leukemic cell line and that the particular PTPase, F-36-12, might be involved in the differentiation process in HL60 cells.
Leukemia 1993 May
PMID:Identification of novel protein-tyrosine phosphatases in a human leukemia cell line, F-36P. 848 28

Embryonic hematopoiesis is initiated in part in the blood islands of the yolk sac. Previous confocal microscopic analysis has shown that the CD34 antigen, a mucin-like cell surface glycoprotein that is expressed by hematopoietic progenitors and all endothelial cells of the adult and embryo, is also found on a subset of luminal hematopoietic-like cells in the yolk sac blood islands as well as on the vascular endothelium lining these early hematopoietic locations. We show here that, as in all other hematopoietic sites thus far examined, immunoaffinity-purified CD34+ nonadherent cells from murine yolk sacs contain the vast majority of erythroid and myeloid progenitor cell colony forming activity. To examine the developmental interactions between these CD34+ hematopoietic progenitor cells of the yolk sac and the CD34+ yolk sac endothelium, we have immunaffinity-purified adherent endothelial cells from day 10.5 yolk sacs using CD34 antiserum and produced cell lines by transformation with a retrovirus expressing the polyoma middle T antigen. Analysis of these cell lines for CD34, von Willebrand's factor, FLK 1 and FLT 1 expression, and capillary growth in Matrigel indicates that they appear to be endothelial cells, consistent with their original phenotype in vivo. Coculture of yolk sac CD34+ hematopoietic cells on these endothelial cell lines results in up to a 60-fold increase in total hematopoietic cell number after approximately 8 days. Analysis of these expanded hematopoietic cells showed that the majority were of the monocyte/macrophage lineage. In addition, examination of the cultures showed the rapid formation of numerous cobblestone areas, a previously described morphologic entity thought to be representative of early pluripotential stem cells. Scrutiny of the ability of these endothelial cell lines to expand committed progenitor cells showed up to a sixfold increase in erythroid and myeloid colony-forming cells after 3 to 6 days in culture, consistent with the notion that these embryonic endothelial cells mediate the expansion of these precursor cells. Polymerase chain reaction analyses showed that most of the cell lines produce FLK-2/FLT-3 ligand, stem cell factor, macrophage colony-stimulating factor, leukemia-inhibitory factor, and interleukin-6 (IL-6), whereas there is a generally low or not measurable production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IL-1, IL-3, transforming growth factor beta-1, erythropoietin, or thrombopoietin. The output of mature hematopoietic cells from these cocultures can be modified to include an erythroid population by the addition of exogenous erythropoietin. These data suggest that endothelial cell lines derived form the yolk sac provide an appropriate hematopoietic environment for the expansion and differentiation of yolk sac progenitor cells into at least the myeloid and erythroid lineages.
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PMID:CD34+ endothelial cell lines derived from murine yolk sac induce the proliferation and differentiation of yolk sac CD34+ hematopoietic progenitors. 854 34

An increase in the incidence and severity of bacteremia caused by group A streptococci was noted in 1993 and 1994 in the Hadassah University Medical Center, Jerusalem. During the 6-year period 1987 to 1992, 12 children with group A streptococcal bacteremia were hospitalized, whereas in 1993 and 1994 there were 17 patients, 5 of them with 1 each of the following severe clinical manifestations: meningitis and septic shock; streptococcal toxic shock syndrome; septic shock; pleural empyema; and fatal outcome. Our 29 patients with group A streptococcal bacteremia were younger than those reported in the literature: 10 (35%) were < 3 months of age; 17 (59%) were < 1 year old. Most children were previously healthy and only 3 had an underlying immunodeficiency predisposing to infection (1 case each): leukemia; Di George syndrome; and congenital nephrotic syndrome. Two children were recovering from varicella. The skin was the most common site of primary infection (16 of 29). The average white blood cell (WBC) count was 18 150 cells/mm3 (range, 2200 to 34,200). The cases were not related epidemiologically and were caused by a variety of M-protein types. Polymerase chain reaction amplification of the genes encoding exotoxins A (speA) and C (speC) was done on 19 isolates and disclosed 2 strains positive for speA and 5 positive for speC. One of the speA-positive isolates was from the single patient with toxic shock syndrome.
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PMID:Increased incidence and severity of Streptococcus pyogenes bacteremia in young children. 855 25

We have recently established a new Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) cell line, designated Z-33. This line has L2 morphology, ultrastructural characteristics of lymphoblasts and typical B lineage surface markers identical to those observed in the Ph1-positive ALL patient from whom the line was derived. In addition, a rearranged immunoglobulin heavy-chain gene (JH) band was found in Z-33 cells by Southern blot analysis, confirming B cell clonality. Cytogenetic analysis of the cell line revealed t(9;22)(q34;q11.2). Polymerase chain reaction (PCR)-amplified cDNA from Z-33 cells demonstrated an e1-az BCR-ABL junction, and the p190BCR-ABL protein was detected in them by the immune complex kinase assay. Z-33 cells produce interleukin (IL)-1 beta, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta, Neither IL-1 beta, G-CSF, TNF-alpha, nor their corresponding antibodies affected the cell line's growth. In contrast, anti-GM-CSF neutralizing antibodies suppressed Z-33 colony formation, and GM-CSF stimulated it in a dose-dependent fashion. In addition, receptor studies with biotinylated GM-CSF demonstrated specific binding to Z-33 cells, indicating that the cells express GM-CSF receptors. Taken together, our data suggest that the Ph1-positive Z-33 ALL cells produce GM-CSF, express GM-CSF receptors, and show an autocrine proliferative response to this cytokine.
Leukemia 1996 Sep
PMID:Molecular and biologic characterization of a newly established Philadelphia-positive acute lymphoblastic leukemia cell line (Z-33) with an autocrine response to GM-CSF. 875 77

A clonal-specific polymerase chain reaction technique to detect T-cell receptor delta gene rearrangement in acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL) was evaluated. It was applied to detect minimal residual disease. A sensitive and specific technique to detect minimal residual disease for T-cell malignancies was explored. Southern analysis and polymerase chain reaction (PCR) were used to detect the rearranged V-D-J segment of T-cell receptor delta (TCR delta) gene from malignant cell specimens of patients with leukemia and lymphoma of T-cell lineage. The PCR product was sequenced and from the DNA sequences of the V-D-J region, a 3' anti-sense primer was designed and synthesized for clonal specific PCR (CS-PCR). T-cell receptor delta (TCR-delta) gene rearrangement was studied in 40 cases of acute leukaemia and lymphoma of T-cell lineage at diagnosis. Using Southern analysis, the positive rates were 28 and 32% for the 18 T-lymphoma and 22 T-ALL, respectively. A one stage Polymerase Chain Reaction (PCR) technique was used to detect the rearrangement in Southern positive cases and the PCR positive rates were 80 and 86%, respectively. The PCR technique had a sensitivity of 0.1%. Serial follow-up marrow specimens were available from 4 T-ALL patients following chemotherapy for monitoring of minimal residual disease. Their PCR products were DNA sequenced. A 3' primer was designed for each case for a clonal specific (CS) PCR. The technique had a sensitivity of 0.003%. It was applied to detect minimal residual disease in serial follow-up marrow samples. The first patient had persistent negative CS-PCR results and enjoyed continuous remission for more than 3 years. The second patient with negative one stage PCR but positive CS-PCR results had eventual relapse of leukaemia. The other two patients never achieved a morphological remission. These preliminary results appeared to support the usefulness of these PCR techniques in detecting minimal residual disease and predicting relapses for ALL. However, further clinical correlation in larger populations of patients is necessary.
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PMID:Detection of T-cell receptor delta gene rearrangement in T-cell malignancies by clonal specific polymerase chain reaction and its application to detect minimal residual disease. 875 82

An HTLV-I-seronegative case of adult T-cell leukemia (ATL) carrying the HTLV-I genome is reported. Screening serological tests were negative and Western blot analysis revealed only a faint band for HTLV-I p24. Polymerase chain reaction (PCR) disclosed the presence of HTLV-I gag, pol, env, pX, and LTR sequences in the lymph node and peripheral blood. Southern blot analysis revealed a monoclonal integration of HTLV-I in the lymph node and peripheral blood. The tumor cells expressed viral antigens after short-term culture. The clinical course was consistent with ATL in that the patient exhibited hypercalcemia and abnormal lymphocytosis as well as hepatosplenomegaly and lymphadenopathy. We recommend that PCR analysis for HTLV-I be performed even in seronegative cases when ATL is clinically suspected.
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PMID:HTLV-I-seronegative, genome-positive adult T-cell leukemia: report of a case. 889 40

The incidence of cutaneous atypical mycobacterial infections is increasing. Their clinical presentation is variable. The atypical mycobacteria are difficult to culture and thus diagnosis can be difficult to establish. PCR (Polymerase Chain Reaction) and mycolic acid analysis have recently been used for mycobacterial species identification, but are not routinely used. Risk factors for cutaneous atypical mycobacterial infection include (1) immunodepression due to HIV infection, lymphoma, leukemia or immunosuppressive therapy. Immunodepression is responsible for the emergence of cutaneous infections by a large variety of atypical mycobacterial species, particularly in industrialized countries. (2) The natural environment is directly responsible for the emergence of cutaneous infections but a small number of atypical mycobacterial species including M. marinum in Europe and North America, and M. ulcerans in the tropics. (3) The medical environment when sterilization is inadequate is also not uncommonly responsible. Clinical features are rarely specific for mycobacterial species, and thus analysis of factors relevant to treatment is more important than species classification. We describe environmental forms (Buruli ulcer caused by M. ulcerans is endemic in the tropics, and swimming pool granuloma which is the aquatic form of M. marinum infection), opportunist forms caused by various species in immunodepressed hosts and iatrogenic and accidental forms mostly due to M. fortiutum and M. chelonei. We review the literature and update the clinical characteristics and risk factors for these diseases.
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PMID:[Atypical mycobacterial skin infections]. 899 95

We have measured the efficiencies of utilization of 8-oxo-dGTP and 8-NH2-dGTP by human immunodeficiency virus type 1 and murine leukemia virus reverse transcriptases and compared them to those of DNA polymerases alpha and beta. Initially, we carried out primer extension reactions in the presence of dGTP or a dGTP analog and the remaining three dNTPs using synthetic DNA and RNA templates. These assays revealed that, in general, 8-NH2-dGTP is incorporated and extended more efficiently than 8-oxo-dGTP by all enzymes tested. Second, we determined rate constants for the incorporation of each analog opposite a template cytidine residue using steady state single nucleotide extension kinetics. Our results demonstrated the following. 1) Both reverse transcriptases incorporate the nucleotide analogs; discrimination against their incorporation is a function primarily of Km or Vmax depending on the analog and the enzyme. 2) Discrimination against the analogs is more stringent with the DNA template than with a homologous RNA template. 3) Polymerase alpha exhibits a mixed kinetic phenotype, with a large discrimination against 8-oxo-dGTP but a comparatively higher preference for 8-NH2-dGTP. 4) Polymerase beta incorporates both analogs efficiently; there is no discrimination with respect to Km and a significantly lower discrimination with respect to Vmax when compared with the other polymerases.
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PMID:Incorporation of the guanosine triphosphate analogs 8-oxo-dGTP and 8-NH2-dGTP by reverse transcriptases and mammalian DNA polymerases. 903 7

High efficiency retroviral-mediated gene transfer to rhesus CD4+ peripheral blood lymphocytes (PBL) was accomplished using an optimized transduction protocol using a gibbon ape leukemia virus (GaLV) envelope-containing packaging cell line PG13. Engineered CD4+ PBL were administered to three nonmyeloablated animals in three or four separate infusions over 9 months. Polymerase chain reaction (PCR) demonstrated in vivo reconstitution of the genetically engineered CD4+ PBL at levels between 1% and 10% of the circulating leukocytes. This level of gene marking indicates that up to 30% of endogenous circulating CD4+ cells can be genetically engineered. The high levels of marked lymphocytes persist for the first 3 weeks following reinfusion then decline to < or = 0.1% over the next 21 weeks. Lymph node (LN) biopsies were performed to determine if the engineered CD4+ lymphocytes could traffic to lymphoid tissues. Marked lymphocytes were detected in LN biopsies 100 days following reinfusion of the transduced cells. Expression of retroviral vector-derived sequences was detected by reverse transcriptase (RT)-PCR analysis from CD4-enriched lymphocytes that were activated by culturing in the presence of recombinant interleukin-2 (rlL-2). A humoral immune response to fetal bovine serum (FBS) was detected in all animals following the second administration of the culture expanded CD4+ lymphocytes. No antibody response was detected to the neomycin-resistance (Neo(R)) transgene, the murine retroviral group-specific antigen (gag), or GaLV envelope (env) proteins.
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PMID:Efficient in vivo marking of primary CD4+ T lymphocytes in nonhuman primates using a gibbon ape leukemia virus-derived retroviral vector. 905 20


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