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

Granulocyte colony-stimulating factor (G-CSF) has strong leukopoietic activity and it is used for patients with leukopenia during leukemia chemotherapy. However, some leukemia cells show a high affinity to G-CSF and are driven to proliferative phase. In our laboratory, we developed two testing methods. 1) Flow cytometric method on G-CSF susceptibility of leukemia cells using FITC-labeled G-CSF, and 2) Immunohistochemical method for detecting the ratio of cells driven from dormant phase to proliferative phase by G-CSF with anti-PCNA antibody and Ki-67 antibody. In MDS patients G-CSF administration induced an increase of cells in proliferative phase. The patients treated with cytosine arabinoside following G-CSF showed hematologically good improvement. A new mode of therapy using G-CSF in combination with other cytokines or antileukemic agents will be developed in the near future for treatment of leukemia patients.
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PMID:[Recent trend in G-CSF therapy and clinical laboratory tests]. 128 10

We have investigated proliferation in bone marrow trephine biopsies from 32 patients with normal or abnormal haemopoiesis, using the monoclonal antibody PC10, which detects proliferating cell nuclear antigen (PCNA), together with immunohistochemical markers of haemopoietic cell lineage. PCNA immunostaining revealed the pattern of proliferation within individual haemopoietic lineages in normal marrow. Two unexpected observations were made: of erythroid cells, only pro-erythroblasts and occasional early normoblasts reacted, and positivity of megakaryocytes was unrelated to nuclear lobulation or CD61 expression. The pathological cases represented conditions in which haemopoiesis is increased (reactive hyperplasia, chronic granulocytic leukaemia, myeloproliferative and myelodysplastic syndromes, megaloblastic anaemia). Increases in the number, and disturbances of the spatial organization, of PCNA-expressing cells were present to a variable extent in all cases. Sheets of PCNA-positive megaloblastoid erythrocytes were frequently found in myelodysplastic and myeloproliferative tissue, associated with marked disturbances in the spatial organization of all haemopoietic lineages. Cases of megaloblastic anaemia due to vitamin B12/folate deficiency also demonstrated greatly increased erythroid PCNA expression, with positivity in some giant metamyelocytes. In addition to reflecting increased proliferation, elevated PCNA expression in some bone marrow pathologies may be due to altered kinetics of the protein induced by disturbances in growth factor production.
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PMID:A study of cell proliferation in formalin-fixed, wax-embedded bone marrow trephine biopsies using the monoclonal antibody PC10, reactive with proliferating cell nuclear antigen (PCNA). 134 81

The proliferative activity of bone marrow leukemia cells was determined by DNA flow cytometric (FCM) analysis and labeling index (LI) of Ki-67 monoclonal antibodies and proliferating cell nuclear antigen (PCNA) autoantibodies in 73 children with acute leukemia. LI of Ki-67 varied greatly from patient to patient (range, 0.4% to 42.2%; mean, 18.8%) and differed significantly between acute lymphoblastic leukemia (ALL) and acute nonlymphoblastic leukemia (ANLL). In ALL, the Ki-67 LI showed a positive correlation with the S-phase fraction (SPF) determined by DNA FCM analysis, whereas, in ANLL, there was a discrepancy between the Ki-67 LI and SPF. In contrast, LI of PCNA varied less among the patients (range, 57.2% to 100%; mean, 90.3%), and the value was always higher than that of the Ki-67 LI in individual patients. A significant relationship between PCNA LI and the percentage of blast cells was found in peripheral blood leukocytes from patients with leukemia. These results suggest that the Ki-67 LI reflects differences in the proliferative activity depending on the subtype of the disease and that the PCNA LI is useful as a marker of proliferating cells.
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PMID:Cell proliferation in childhood acute leukemia. Comparison of Ki-67 and proliferating cell nuclear antigen immunocytochemical and DNA flow cytometric analysis. 134 83

To investigate the growth characteristics of human leukemia cells, the expression of proliferation-associated nuclear antigens was examined in relation to cell cycle phases in marrow blast cells obtained from 37 untreated children with acute leukemia. Ki-67 monoclonal antibody reactive antigen and proliferating cell nuclear antigen (PCNA) were measured by the simultaneous flow cytometric analysis of DNA and nuclear antigens. The percentage of PCNA-positive cells was always higher than that of Ki-67-positive cells in individual patients. The level of PCNA was greatly increased in G1 or early S phase, but was generally stable in S and G2 phases. Accordingly, most of the cells in the proliferative compartments (greater than 2C DNA) showed a high expression of PCNA. In contrast, expression of Ki-67 antigen varied greatly from patient to patient, and differed significantly in different subtypes of the disease. The level of Ki-67 antigen increased with the cell cycle progression, showing maximum expression in late S and G2 phases. However, in most of the patients, a distinct population of Ki-67-negative cells was found not only in G1 phase, but also in the proliferative compartments. These results appear to reflect differences in the proliferative activity of bone marrow blast cells in childhood acute leukemia.
Leukemia 1992 Jul
PMID:Cell-cycle-associated expressions of proliferating cell nuclear antigen and Ki-67 reactive antigen of bone marrow blast cells in childhood acute leukemia. 135 61

The BCL-2 (B-cell lymphoma/leukemia-2) gene is frequently involved in t(14;18) translocations in non-Hodgkin's lymphomas and encodes a 26-kDa intracellular, membrane-associated protein. Expression of the BCL-2 gene has previously been correlated with cellular proliferation in normal and neoplastic lymphoid cells under a variety of experimental conditions. To examine the regulation of p26-BCL-2 protein levels during the cell cycle, we utilized the method of counterflow centrifugal elutriation to enrich for cells in various phases of the cell cycle. Relative levels of p26-BCL-2 protein were measured by immunoblotting, and comparisons were made with a cell cycle-regulated protein, p62-CYCLIN-A, and a protein whose levels are constant throughout the cell cycle, p36-PCNA (DNA polymerase-delta auxiliary factor). Relative levels of p26-BCL-2 and p36-PCNA did not vary among cell fractions enriched for specific phases of the cell cycle, whereas p62-CYCLIN-A was elevated in late S- and G2/M-phase cells. Similar results were obtained with lymphoma and leukemia cell lines that have either normal or translocated BCL-2 genes. These results obtained by elutriation were confirmed by pharmacologically inducing cell cycle arrest in proliferating lymphoid cell lines with hydroxyurea, quercetin, and nocodazole which blocked cells at S, G2, and M phases, respectively. Taken together, the data indicate that p26-BCL-2 is not a true cell cycle-regulated protein, although its levels can fluctuate in connection with changes in rates of cellular proliferation under some circumstances.
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PMID:Cell cycle analysis of p26-BCL-2 protein levels in proliferating lymphoma and leukemia cell lines. 158 93

The action of 3'-azido-3'-deoxythymidine 5'-triphosphate (N3dTTP) on DNA strand elongation catalyzed by human immunodeficiency virus type 1 reverse transcriptase was evaluated in comparison with human DNA polymerase alpha and proliferating cell nuclear antigen-independent DNA polymerase delta. Sequencing gel analysis demonstrated that the human immunodeficiency virus 1 reverse transcriptase preferentially incorporated N3dTTP into the T sites of the growing DNA strands and caused chain termination in a dose-dependent manner. This effect was observed even when the N3dTTP concentration was 0.3 microM, 100-fold less than dTTP. Studies with reverse transcriptases from avian myeloblastosis virus and Moloney murine leukemia virus showed that N3dTTP was also efficiently incorporated into DNA by these enzymes and terminated DNA strand elongation. In contrast, human DNA polymerases alpha and delta did not incorporate detectable amounts of N3dTTP into the DNA and were not inhibited by 300 microM N3dTTP. The selective incorporation of the chain-terminating nucleotide by the viral reverse transcriptases appears to be a molecular basis for the positive therapeutic index of 3'-azido-3'-deoxythymidine.
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PMID:Selective action of 3'-azido-3'-deoxythymidine 5'-triphosphate on viral reverse transcriptases and human DNA polymerases. 169 49

We recently found that inhibition of MYB protein synthesis in human peripheral blood mononuclear cells (PBMC) exposed to human c-myb (designated MYB) antisense oligodeoxynucleotides prevents entry into S phase and cell proliferation. To determine the mechanism(s) by which down-regulation of human c-myb protein (MYB) synthesis interferes with DNA synthesis, we analyzed mRNA levels of DNA polymerase alpha and proliferating cell nuclear antigen (PCNA), transcripts of two genes required for DNA synthesis, in normal and leukemic T lymphocytes exposed to MYB antisense oligodeoxynucleotides. Expression of DNA polymerase alpha was inhibited both in normal T lymphocytes progressing from G0 to S phase and in exponentially growing CCRF-CEM leukemic cells, whereas expression of PCNA was inhibited only in mitogen-stimulated PBMC and remained essentially unaffected in the leukemia T-cell line. The functional link between expression of MYB and DNA polymerase alpha mRNAs was further demonstrated by analyzing DNA polymerase alpha mRNA levels in a temperature-sensitive (ts) fibroblast cell line (TK-ts13; TK is thymidine kinase) constitutively expressing human MYB mRNA driven by the simian virus 40 (SV40) promoter. In the MYB-expressing TK-ts13 cells, DNA polymerase alpha mRNA levels were unaffected following shift to the nonpermissive temperature of 39.6 degrees C, whereas in the parental line, DNA polymerase alpha mRNA levels were readily down-regulated. These findings indicate that the expression of MYB is related to that of DNA polymerase alpha in cells expressing MYB at high levels and suggest that there is a functional link between c-myb and DNA polymerase alpha mRNA expression during cell cycle progression of normal T lymphocytes.
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PMID:Inhibition of T-cell proliferation by a MYB antisense oligomer is accompanied by selective down-regulation of DNA polymerase alpha expression. 169 13

Histopathologic diagnosis of the bone marrow in leukemia is usually a supplementary method to the cytological in acute and chronic leukemia. However, for patients with MDS and MPD and with dry tap bone marrow biopsy is very important. Important morphological findings and useful immunohistochemical methods for differentiation and characterization of leukemia are reported and the usefulness of sequential examination of bone marrow in leukemia during and after chemotherapy is emphasized. In addition to leukemia, histological features and differential points of myelodysplastic syndrome (MDS) and myeloproliferative disorders (MPD) are mentioned. The proliferating megakaryocytes differed in size and shape between MDS and MPD. The difference in proliferating rate of the cells examined by PCNA was also useful to differentiate the two disorders histologically.
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PMID:[Histopathologic diagnosis of bone marrow in leukemia and related disorders]. 177 61

We investigated whether the proliferating cell nuclear antigen (PCNA) protein takes part in cis-diamminedichloroplatinum (II) (CDDP) resistance, using a murine leukemia cell line P388 and its CDDP resistant cell line. P388/CDDP was 4 times more resistant to CDDP than P388. The cell lines were maintained in the DBA/2 female mouse peritoneal space. In total cells, the amount of the PCNA protein decreased to 90% in P388 after 1 h CDDP treatment, but that of P388/CDDP increased to 127%. The difference was statistically significant (p = 0.012, n = 5). As for G2/M phase cells, the difference was also significant at 1 h (p = 0.016, n = 5) and at 2 h (p = 0.036, n = 5) after treatment. In P388 the amount of the PCNA protein decreased in accordance with the inhibited cell proliferation, whereas in P388/CDDP, the amount of the PCNA protein increased in spite of the inhibited cell proliferation. This increase of the PCNA protein suggests that the PCNA protein is involved in CDDP resistance of P388/CDDP through enhanced DNA repair synthesis.
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PMID:The relationship of the proliferating cell nuclear antigen protein to cis-diamminedichloroplatinum (II) resistance of a murine leukemia cell line P388/CDDP. 202 4

Double immunofluorescence and [3H]thymidine autoradiographic analysis of the same field of transformed human amnion cells (AMA) reacted with proliferating cell nuclear antigen (PCNA) autoantibodies and a monoclonal antibody (mAb 19F4) specific for cyclin (PCNA) revealed similar patterns and sequence of cyclin (PCNA) antigen staining during S-phase. These results suggest that immunofluorescence patterns obtained with PCNA autoantibodies reflect in fact patterns of cyclin (PCNA) antigen staining.
Leukemia 1987 Mar
PMID:PCNA (cyclin) autoantibodies and monoclonal antibodies reveal similar patterns of cyclin (PCNA) antigen staining in human cultured cells. 288 55


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