Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Terminal deoxynucleotidyl transferase (TDT) is an unusual DNA polymerase that does not use template information to synthesize new strands of DNA. It is normally found in high concentration in thymus (50 u/10(8) cells) and in low concentration in bone marrow (less than 5 u/10(8)). We report TDT measurements in the marrow and/or peripheral blood of 51 adult patients, 28 of whom had leukaemia. TDT is present in very high levels (greater than 50 u/10(8) cells) in leukaemic lymphoblasts and in low levels in leukaemic myeloblasts (less than 9 u/10(8) cells). Of two patients who developed lymphosarcoma-cell leukaemia following treatment of poorly differentiated lymphocytic lymphoma, one had high and one low levels of TDT in the leukaemic blast cells. Leukaemic cells from three of seven patients with chronic myeloid leukaemia in blast crisis had TDT levels within the range expected of acute lymphoblastic rather than acute myeloid leukaemia. High TDT in leukaemic cells probably marks them as derivatives of lymphoid progenitor, thymic or pluripotential stem cells. Quantitative assay of TDT may provide information useful in classifying haematological neoplasms.
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PMID:Terminal deoxynucleotidyl transferase measurements in the differential diagnosis of adult leukaemias. 6 84

The myelogenous leukemia cell line K-562 with a Ph1+chromosome, derived from a patient with chronic myelogenous leukemia in terminal blastic crisis, is not a bone marrow-derived lymphoblastic cell line, because the cells neither produce immunoglobulins nor possess complement receptors. Since it has been suspected that blasts found in some patients with chronic myelogenous leukemia in blastic crisis might be thymus-derived cells, we have studied several parameters to demonstrate that K-562 cells are not thymus-derived lymphoblasts. The results of this study show: (a) no cross-reactivity of antisera to K-562 cells with normal human thymocytes; (b) lack of cytotoxicity of a specific horse anti-human thymocyte globulin for K-562 cells; (c) failure of the treatment of K-562 cells with bovine thymosin to induce antigenic determinant and erythrocyte rosette receptors on K-562 cells; (d) presence of receptors for the Fc portion of immunoglobulin G; (e) absence of terminal deoxynucleotidyl transferase; and (f) cytotoxicity of monkey antiserum to K-562 cells for malignant thymus-derived cells (Molt-4). However, absorption with Molt-4 cells abolished the cross-reactivity with Molt-4 cells, whereas 60% of the antibody to K-562 cells remained in the immune serum. Studies of DNA polymerase activities revealed that K-562 cells have levels of polymerase alpha and beta, like other proliferating cells, and an RNA-dependent DNA polymerase activity, presumably representing polymerase gamma.
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PMID:Absence of thymus-derived lymphocyte markers in myelogenous leukemia (Ph1+) cell line K-562. 6 24

A new technique which detects the presence of DNA polymerase and primer-template DNA by measuring the incorporation of 3H-thymidine-5-triphosphate (3H-TTP) showed cytoplasmic labelling of eosinophilic granulocytes and eosinophilic myelocytes in normals, in acute leukaemia, in chronic myeloid leukaemia and in patients with eosinophilia of unknown origin.
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PMID:Cytoplasmic labelling of eosinophils with tritiated thymidine triphosphate. 28 22

Proliferative cell fractions were measured by flow cytometry in 20 patients with acute leukemia, 4 with chronic myelocytic leukemia in blastic crisis and 7 with malignant lymphoma. The cells were fixed with 2% paraformaldehyde followed by staining with fluorescein isothiocyanate conjugated monoclonal antibody against DNA polymerase a. The DNA polymerase a-positive population was widely distributed in leukemia, from 20.4% to 84.7% in peripheral blood and from 6.5% to 92.5% in the bone marrow. A positive correlation was found between the values in peripheral blood and bone marrow. The values ranged from 66.4% to 88.1% in cells from cases of malignant lymphoma. Cryopreserved cells may be available for measurement of DNA polymerase a because the result obtained in both frozen and fresh cells were essentially the same.
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PMID:[Detection of proliferative cells by DNA polymerase a as a proliferation associated marker]. 144 3

Among 262 inpatients with hematologic diseases who were referred for chemotherapy or immunosuppressive therapy between January, 1985, and December, 1989, nine (3.4%) patients, including two with Hodgkin's disease (HD), three with acute myeloblastic leukemia, one with chronic myelogenous leukemia, two with multiple myeloma and one with aplastic anemia, were found to be hepatitis B virus (HBV) carriers before their chemotherapy began. All six HBV carriers who received chemotherapy containing glucocorticoid showed mild-to-moderate elevations in serum transaminase levels after the chemotherapy. Five showed a rise in titer of the hepatitis B surface antigen, HBsAg. In contrast, three HBV carriers not receiving glucocorticoid showed no change in serum transaminase after chemotherapy. One HBV carrier with HD suffered from severe icteric hepatitis after the withdrawal of multiagent chemotherapy containing glucocorticoid. The HBV-DNA polymerase rose markedly and was accompanied by a marked rise in titer of HBsAg. The results warn us to keep in mind the possibility of glucocorticoid inducing an activation of HBV infection, which may result in severe hepatitis in some HBV carriers. Although further investigation is required, it is recommended that HBsAg-positive patients with hematologic malignancies should, if possible, be treated without glucocorticoid.
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PMID:Activation of hepatitis B virus infection by chemotherapy containing glucocorticoid in hepatitis B virus carriers with hematologic malignancies. 175 16

The human multidrug-resistance gene (MDR1) encodes an energy-dependent multidrug efflux protein responsible for the cross-resistance of cultured cells to natural product chemotherapeutic agents such as the anthracyclines and vinca alkaloids. RNA transcript levels were measured in leukemia cells obtained from 15 adult acute nonlymphocytic leukemia (ANLL) cases and 15 cases of chronic myelogenous leukemia (CML). Expression of MDR1 RNA was common in ANLL, and appears to be most frequent in leukemic cells of patients with the poorest response to chemotherapy. Expression of the MDR1 gene was not detectable in the peripheral white blood cells of any of the CML cases during the chronic phase, but was detectable in the immature cells present during this phase of the disease. The cells of the three blastic crisis patients contained detectable levels of MDR1 RNA. These studies support the idea that expression of the MDR1 gene contributes to drug resistance in ANLL, and may play a role in some instances in the drug-resistance of CML in blastic crisis. In contrast, studies of the level of expression of anionic glutathione transferase and DNA polymerase B failed to show any relationship between the RNA transcript levels of these enzymes and responsiveness to chemotherapy.
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PMID:Expression of the multidrug resistance gene in myeloid leukemias. 230 54

Chronic myelogenous leukemia (CML) is a stem cell disease which, on a clinical level, progresses from the release from growth control of normally differentiated cells (a preleukemic state) to an acute leukemia. On a molecular level, the evolution of CML to acute leukemia is a multistep process. We propose that an early step, at the stem cell level, is acquisition of the ability for gene movement, which allows subsequent submicroscopic and chromosomal rearrangements that cause changes in the growth characteristics and regulation of the stem cell. A specific platelet DNA polymerase (PDP - reverse transcriptase) may play a role in gene movement. The characteristic reciprocal translocation of chromosomes #9 and #22, causing the activation of the c-abl oncogene, appears to be responsible for the uncontrolled cellular growth. Yet, other growth factors (e.g., platelet derived growth factor) and activated oncogenes (e.g., c-sis) must be responsible for the stimulation, progression, and variability seen during the course of the disease. Because CML is a progressive disease with clinically definable stages, CML appears to be a model system for the study of the molecular basis of the progression of preleukemia to leukemia specifically, and preneoplasia to aggressive neoplasia in general.
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PMID:Implications of retroviral and oncogene activity in chronic myelogenous leukemia. 243 4

Partially purified platelet DNA polymerase (PDP) was able to synthesize DNA transcripts of platelet polyadenylated RNA. PDP was elevated in the earliest stages of CML and PV. In PV, successful chemotherapy resulted in rapid return of PDP to normal levels while in CML this was not the case. An hypothesis is presented proposing that PDP contributes to oncogenesis by regulating the expression of oncogenes.
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PMID:Platelet DNA polymerase levels in CML: implications for oncogenesis. 620 35

Terminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase which is only found in immature cells of lymphoid lineage (pre-T/pre-B). Because of this restricted distribution of TdT, biochemical and immunofluorescence techniques have been employed to determine the distribution of TdT phenotypes in human leukemias and lymphomas, showing high levels of TdT in approximately 95% of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL), approximately 50% of patients with acute undifferentiated leukemia (AUL), approximately 10 of patients with acute nonlymphoblastic leukemia (ANLL), and approximately 30% of patients with chronic myeloid leukemia (CML) and other myeloproliferative (MPS) or myelodysplastic (MDS) syndromes in blast crisis. High levels of TdT activity are associated with a clinical response to remission inducing therapy with vincristine and prednisone in a high proportion of patients (50%-90%), irrespective of clinical and morphologic diagnosis. Preliminary studies furthermore suggest that TdT might serve as a sensitive indicator of subclinical disease in ALL in complete remission.
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PMID:Methods and clinical relevance of terminal deoxynucleotidyl transferase determination in leukemic cells. 694 40

Terminal deoxynucleotidyl transferase is a unique DNA polymerase that can carry out DNA synthesis on an initiator molecule in the absence of a template. The usefulness of this enzyme as a biological marker for following patients during treatment and remission has been suggested. The potential usefulness of this enzyme in predicting the onset of relapse before any morphological indications has been demonstrated in chronic myelogenous leukemia patients in blast phase of the disease. In order to be able to detect low levels of TdT activity especially during remission phase, we have used cell separation techniques which can enrich cell populations containing TdT activity. A number of cell separation techniques have been developed to separate different cell types. We have used the techniques of unit gravity sedimentation and free flow electrophoresis to achieve enrichment of TdT positive cell populations. Our results show that up to 20 fold enrichment of TdT activity in normal human bone marrow can be accomplished by using cell separation techniques. With the use of free flow electrophoresis, we have achieved enrichment of TdT positive cell populations from normal human bone marrow, cells from patients with acute lymphoblastic leukemia and chronic myelogenous leukemia in blast phase of the disease. No TdT positive cells were detected in patients with acute myelogenous leukemia. These cell separation techniques should prove to be useful in early detection of relapse in patients in remission.
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PMID:Enrichment of terminal deoxynucleotidyl transferase activity by cell separation. 698 Dec 92


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