phosphorus-radioisotopes and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Topics: Animals; Base Sequence; Drug Carriers; Fluorescent Dyes; HL-60 Cells; Humans; Indicators and Reagents; K562 Cells; Kidney; Liposomes; Liver; Male; Mice; Mice, Inbred ICR; Microscopy, Fluorescence; Oligodeoxyribonucleotides, Antisense; Phosphorus Radioisotopes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radioisotope Dilution Technique; Rats; Rats, Inbred Lew; Tissue Distribution; Tumor Cells, Cultured

Essential thrombocythemia is a myeloproliferative disorder that infrequently evolves into acute leukemia. Leukemic transformation is frequently preceded by therapy with alkylating agents or radioactive phosphorus (32P), and is virtually always myeloid in nature. In this report, the authors describe a case of acute lymphoblastic leukemia arising in a patient with long-standing essential thrombocythemia.

Topics: Aged; Antigens, CD; Blast Crisis; Bone Marrow; Female; Humans; Hydroxyurea; Lymphocyte Activation; Phosphorus Radioisotopes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thrombocytosis

The distribution of primer RNA and RNA-primed nascent DNA in nuclei of CCRF-CEM leukemia cells was examined, and the primer RNA purified from the nuclear matrices of these cells was characterized. RNA-primed nascent DNA was radiolabeled by incubating whole-cell lysates with [alpha-32P]ATP and [3H]dTTP in the presence of approximately physiological concentrations of the remaining ribo- and deoxyribonucleoside triphosphates. The primer RNA was purified by cesium chloride density gradient centrifugation and analyzed by polyacrylamide gel electrophoresis. Nuclear subfractionation studies revealed that at least 94% of the primer RNA and RNA-primed nascent DNA were located within the insoluble matrix fraction of the nucleus. The predominant primer RNA isolated from the nuclear matrix was 8-10 nucleotides in length, and several lines of evidence indicated that this oligoribonucleotide was the functional primer RNA. Essentially all of the matrix primer RNA was covalently linked to the newly replicated DNA as demonstrated by its buoyant density in cesium chloride gradients, phosphate-transfer analysis, and sensitivity to DNase I. Analysis of 32P transfer from [alpha-32P]dTTP revealed a random distribution of ribonucleotides at the 3'-end of the primer RNA. Data obtained from mixing experiments indicated that the association of RNA-primed nascent DNA with the nuclear matrix was not the result of aggregation of these fragments with the nuclear matrix. No significant amount of either primer RNA, RNA-primed nascent DNA, or phosphate transfer was detected in the high-salt-soluble (nonmatrix) fraction of the nucleus, although the nonmatrix fraction contained most of the newly replicated DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Autoradiography; Cell Line; Centrifugation, Density Gradient; DNA, Neoplasm; Electrophoresis, Polyacrylamide Gel; Humans; Kinetics; Molecular Weight; Phosphorus Radioisotopes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radioisotope Dilution Technique; RNA, Neoplasm; Thymine Nucleotides; Tritium; Tumor Cells, Cultured