Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitotic indices, labeling indices (LI), and tritiated thymidine incorporation into DNA of marrow cells were conducted in patients with leukemia to determine if correlations existed between kinetic measurements, clinical features, and response to chemotherapy. Higher proliferative activity was observed in chronic granulocytic leukemia (CGL) and blastic phase of CGL than in acute leukemia. In acute myelogenous leukemia there was no correlation with various clinical features studied. Those patients demonstrating greater than 60% reduction in circulating leukemia cells within 7 days had a higher initial LI than those with less than 60% reduction. Cytosine arabinoside, methotrexate, and hydroxyurea were investigated to determine their synchronizing capability; cytosine arabinoside and methotrexate were superior to hydroxyurea. In a cycle-sensitive schedule specifically designed to synchronize cells, responses occurred more frequently in patients who increased thier LI 48 hours after priming doses of cytosine arabinoside. In an intensive-chemotherapy schedule which produced more remissions than the cycle-sensitive schedule, there was no relationship between initial kinetic measurements and response. Kinetic values increased as patients achieved remissions.
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PMID:Synchronization with phase-specific agents in leukemia and correlation with clinical response to chemotherapy. 102 39

Specific Activities of DNA-dependent RNA polymerases A and B have been determined in nuclei from leukocytes in acute and chronic leukemia. Enzyme activities, dependent on exogenous DNA template, were determined in homogenates of nuclei from isolated mononuclear cells or from isolated granulocytes. Activities of polymerases A and B have been found significantly elevated in homogenates of nuclei from mononuclear cells in acute myelocytic leukemia, while they were found subnormal in corresponding cell fractions from chronic myelocytic leukemia and chronic lymphatic leukemia. During cytostatic treatment polymerase activities were approaching normal values. The prognostic relevance of these data for the course of human leukemia is discussed.
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PMID:[DNA-dependent RNA polymerases in human leukocytes. II different specific activities of the polymerases A and B in acute and chronic leukemia and their prognostic relevance (author's transl)]. 105 88

A technique which detects the presence of DNA-polymerase in cell nuclei by measuring the incorporation of 3H-thymidine-5-triphosphate (3H-TTP) has been used to estimate the proportion of leukaemic myeloblasts which contains DNA-polymerase and DNA capable of acting as primer-template. In six cases of previously untreated acute myeloid leukaemia the 3H-TTP labelling index (3H-TTP LI) was much larger than the fraction in DNA synthesis. After a single 'flash' injection of cytosine arabinoside a pronounced decline was observed in the 3H-TTP LI, which can be explained by a direct inhibition of NDA-polymerase. No change was observed in the fraction of cells labelled with 3H-thymidine. A decrease in 3H-TTP LI was also observed after a single i.v. dose of methotrexate.
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PMID:Nuclear DNA-polymerase estimation in human leukaemic myeloblasts. 106 33

The kinetics of erythropietic and granulocytopoietic cell proliferation have been investigated in the same patient at two distinct stages: firstly in preleukemia presenting as pancytopenia with ineffective erythropoiesis, and secondly 2 years later in acute myelogenous leukemia. The method investigation is based on determining the DNA synthesis rate of individual cells by means of quantitative 14C-autoradiography after short-term incubation with 14C-thymidine and fluorodeoxyuridine. Erythropoiesis was equally ineffective in the two stages, the rate of proliferation, however, slowed down towards the leukemic state. The production rate of myeloblasts was markedly reduced in preleukemia accompained by a very low labelling index. In leukemia on the other hand the production rate was increased to such a degree that the leukemic myeoblast compartment is to be considered as prevailingly self-reproductive. The proliferation rate of myeloblasts was reduced already in preleukemia, and there was a further decrease in leukemia. From the point of view of cell kinetics the manifestation of leukemia in this patient is explained best by a change in the mode of proliferation: the myeloblasts change from steady state growth to behaving like an exponentially expanding population.
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PMID:Proliferation and production of hemopoietic cells two stages of disease: preleukemia and overt leukemia. 106 31

Measurement of in vitro and in vivo resistance to daunorubicin in AML patients suggests that there is no simple correlation between the two. In a patient who became clinically resistant and whose cells showed a parallel increased resistance in vitro we found the acquisition of multiple drug resistance. The increased in vitro resistance to daunorubicin could to some extent be overcome by conjugating daunorubicin to DNA.
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PMID:Acquired resistance to daunorubicin in a patient with acute myelogenous leukaemia. 106 48

Stored autologous haemopoietic cells may be used to repopulate the bone marrow of patients in the advanced stages of different leukaemias who have received cytotoxic drugs. We have used a continuous flow blood cell separator to collect peripheral blood leucocytes from patients with chronic granulocytic leukaemia (CGL) before treatment. We also collected bone marrow cells from patients with CGL and from patients with acute myeloid leukaemia in complete remission. The collected cells were frozen at I degree C per minute using dimethyl sulphoxide as cryoprotective agent and stored in liquid nitrogen. For reconstitution of frozen cells we found that the use of dextran II0 inhibited leucoagglutination. The viability and function of the reconstituted leucocytes were assessed by their morphological appearance, their capacity to phagocytose and kill Candida albicans organisms, their ability to reduce the dye nitroblue tetrazolium (NBT) in vitro and to incorporate tritiated thymidine into DNA and by the growth of colony forming units (CFUc) in agar culture. With this method of cryopreservation the phagocytic function of mature neutrophils is retained to some extent but their capacity to reduce NBT and their microbicidal activity are completely lost. In contrast CFUc may remain after storage for periods of at least 2 years.
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PMID:The cryopreservation of leukaemia cells: morphological and functional changes. 106 49

Hemopoietic cell proliferation was studied in a patient suffering from preleukemia characterized by peripheral pancytopenia and hypercellular bone marrow with ineffective erythropoiesis. Two years later when overt acute myelogenous leukemia had developed the study was repeated. The kinetics of proliferation were investigated by a new method which allows evaluation of the rate and time of DNA synthesis in individual morphologically defined cells. Erythropoiesis was found ineffective to the same degree in both stages of disease. The rate of erythroid cell proliferation, however, was reduced in overt leukemia only. The myeloid system showed a grossly reduced production rate of myeloblasts in preleukemia whilst the same parameter was strongly increased in leukemia. This high production rate of myeloblasts in overt leukemia was interpreted as indication of a far-reaching self-maintenance of the myeloblast pool in this stage of disease. The proliferative activity of the individual myeloblasts was reduced already in preleukemia, and even more so in leukemia. In order to explain the amplification of the myeloblast pool with the onset of overt leukemia a change in the mode of myeloblast divisions is assumed. For this a transition from steady state to some degree of exponential growth gives the most plausible explanation.
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PMID:Proliferative behavior of hemopoietic cells in preleukemia and overt leukemia observed in one patient. 107 Apr 63

The relationship between changes in the bone marrow labeling index and the patient's subsequent response to cycle-specific agents was studied by the South-eastern Cancer Study Group in adults with acute leukemia. Ninety-eight patients were randomized to one of two treatment regimens. Schedule 1 consisted of a single intravenous (i.v.) push of cytosine arabinoside followed in 48 hours by a large dose of oral methotrexate distributed over 24 hours and i.v. vincristine. Leucovorin rescue was employed to control the toxic effects of the high dose methotrexate and the cycle was repeated every 7 days. Schedule 2 differed only in that there were three daily injections of cytosine arabinoside preceding vincristine and methotrexate injections and each cycle was given every 10 days. Cell kinetic studies were performed in 30 patients and revealed that the majority of patients who had a response to therapy had some increase in the marrow labeling index 48 hours after cytosine arabinoside injection. In general, those patients who had no response to therapy had little change. There was no significant difference between schedules in the ability to induce an increase in labeling index 48 hours after cytosine arabinoside or in the increment achieved by the responders. However, there was a significant difference in the response rate seen with these schedules. Schedule 1 achieved only a 24% remission rate in acute nonlymphocytic leukemia (ANLL) while schedule 2 was associated with a 52% remission rate. In acute lymphoblastic leukemia (ALL) both schedules induced a 60% remission rate while none of the four patients with blast crisis of chronic granulocytic leukemia (CGL) responded. Analysis of the characteristics associated with remission revealed that more females achieved a remission than males and that the presence of pretreatment infection was the greatest contributing cause of early death and thus severely limited the ability to achieve a remission. As opposed to the current regimens used in ANLL, schedule 2 did not require significant bone marrow hypoplasia (as judged by the degree of hematological toxicity) to achieve a remission and there was no decrease in response seen with increasing age. The data suggest that increased efficiency of cycle-specific, antitumor agents may occur by increasing the proportion of human leukemic cells in DNA synthesis.
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PMID:An attempt at synchronization of marrow cells in acute leukemia: relationship to therapeutic response. 108 65

Although leukocytes from all 13 acute lymphoblastic leukemia patients examined had high terminal deoxynucleotidyl transferase (terminal transferase) activity (20 to 100 units/mg of cellular DNA, where 1 unit equals 1 nmole of nucleotide polymerized in 1 hr) and those from 21 acute myelocytic leukemia patients had low terminal transferase activity (0.2 to 2 units/mg of cellular DNA), the bone marrow and peripheral blood leukocytes from 2 patients with acute myelocytic leukemia, diagnosed on the basis of clinical features and the morphology, cytochemistry, and cytogenetics of the leukemic cells, had terminal transferase activity (39 to 52 units/mg of cellular DNA) equivalent to that found in leukemic lymphoblasts. These results bring under question the specificity of high terminal transferase activity outside of the thymus as a marker for leukemic lymphoblasts and, secondarily, the derivation of acute lymphoblastic leukemia cells in all cases from thymocytes. Perhaps malignant transformation in a pleuripotent stem cell with derepression of the genome for terminal transferase could account for high terminal transferase activity observed in certain leukemic cells.
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PMID:High terminal deoxynucleotidyl transferase activity in acute myelogenous leukemia. 108 95

217 sera from 33 patients with acute myeloid leukemia (AML), 42 with chronic myeloid leukemia (CML), 12 with acute lymphatic leukemia (ALL), 22 with lymphoma, and 20 with other malignant diseases were examined by a radioimmunological technique for the presence of antibodies against DNA. The levels of single-stranded DNA binding activity was significantly higher in all 3 types of leukemia and lymphoma compared to those of healthy controls. In contrast, none of these sera exhibited a positive reaction with double-stranded DNA. In some cases of leukemia, the level of serum anti-DNA antibodies increased after the decrease of the leukocytes count.
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PMID:Anti--DNA antibodies in patients with leukemia and lymphoma. 108 60


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