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)

Optimized biochemical assays and cytoimmunofluorescence tests were used to detect terminal deoxynucleotidyl transferase, TdT, in malignant cells of 36 leukemias and 75 lymphomas from patients not receiving chemotherapy. TdT was virtually absent from normal lymph nodes and from leukocytes of chronic lymphocytic leukemia, CLL, taken as controls. Its quantitative distribution in the neoplasms matched the current knowledge. Appreciable amounts of TdT were found in all the 10 lymphomas of lymphoblastic type, LL, and in the white blood cells of: 16 out of 19 acute lymphoblastic leukemia, AAL, perhaps with modulation in the various phenotypes; 2 out of 3 acute undifferentiated leukemias, AUL; and 3 out of 7 blastic crises in chronic myelogenous leukemia, b.c. CML. Biochemical and cytoimmunological analyses yielded concordant responses and even roughly comparable estimates in the same patients. TdT immunofluorescence was clearly nuclear in most cells and was cytoplasmic occasionally. Definite correlations between concentrations of enzymatic activity and percentage of immunofluorescent cells could not e established. Further detailed work will be required to identify putative subgroups in TdT-positive blast populations.
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PMID:Studies of terminal deoxynucleotidyl transferase in normal and neoplastic human cells. 681 Jun 61

We describe a relatively simple and rapid assay for DNA nucleotidylexotransferase (EC 2.7.7.31) activity in normal lymphocytes and leukemic cells from blood and (or) bone marrow of patients with various types of leukemia. We followed the method of Beutler and Kuhl (Am. J. Clin. Pathol. 70: 733, 1978) but separated the product of the reaction by precipitation on filter-paper disks instead of by centrifugation. Normal lymphocytes had a mean activity of 13.5 (SD = 9.21; range 3 to 35) pU/10(8) cells. Leukemic cells from the peripheral blood of patients with acute myelogenous leukemia had a mean activity slightly greater than normal (48 pU/10(8) cells); those from patients with acute lymphoblastic leukemia had a mean activity of 863 pU/10(8) cells, or 62-fold the normal mean. Similarly, cells from patients with chronic myelogenous leukemia in acute phase had a normal activity when the cell proliferation was myelogenous, but much higher activities when the cell proliferation was lymphoblastic. Cells from patients with chronic lymphocytic leukemia had normal activity. In leukemic patients, approximately similar results were obtained with cells isolated from bone marrow.
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PMID:DNA nucleotidylexotransferase of normal persons and leukemic patients. 692 45

A micromethod for the determination of TdT in peripheral leukocytes and bone marrow cells has been developed that allows unequivocal identification and quantitation of TdT in less than 1 X 10(6) leukocytes from ALL patients, i.e., in 1 ml of peripheral blood and/or 0.5 ml of bone marrow obtained during routine clinical sampling. The method involves disruption of cell pellet with high salt and detergent followed by centrifugation of extracts at 12,000 X g and partial purification on phosphocellulose matrix by a batch elution technique using a standard laboratory microcentrifuge. Using this microassay, TdT activities have been determined in 500 samples of peripheral blood and bone marrow of 240 adult patients with acute leukemias (86 ALL, 108 ANLL, 44 blastic CML, two acute leukemias following P. vera). From an analysis of our data based on TdT activity, cell surface markers and growth patterns in soft agar and observations published in the literature, it can be concluded that the frequencies of TdT + phenotypes in the various clinical-morphological diagnostic groups are approximately 95% in ALL, 10% in ANLL, 50% in AUL, and 35% in blastic CML. Since the presence of high TdT activity is clearly associated with clinical response to specific forms of chemotherapy in blastic CML and most probably, also in ANLL, the determination of TdT should be considered in all cases of acute leukemias to objectively define prognostically important subgroups which can not be diagnosed by conventional means.
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PMID:A micromethod for determination of terminal deoxynucleotidyl transferase (TdT) in the diagnostic evaluation of acute leukemias. 693 16

Surface marker analyses and TdT assays were performed on cells from 31 patients. A variety of diagnoses were made and categorized as follows: acute leukemia (group I), non-Hodgkin lymphoma (group II) and diverse diagnoses (group III). Levels of TdT in the range from 0 to 7.9 U/mg lyophilized blasts from the peripheral blood were found in AL. This corresponds to 0-95 U/10(8) cells. Preparations of mononuclear cells from the peripheral blood of healthy donors showed TdT values up to 0.88 U/mg or 10.6 U/10(8) cells. High TdT activity was observed in a patient with AML, type M1 according to the FAB classification. In a patient with ALL (L1) cytostatic treatment effected the clearance of TdT activity from the peripheral blood cells and at the same time induced a significant increase of E rosette forming cells. Combined studies of the TdT activity and cell surface markers may enable us to define remissions and relapses of AL more precisely than it is possible by conventional cytological methods. Within the group II two patients with moderate TdT activities of 1.2 and 1.28 U/mg, respectively, were observed whose cells were of prolymphocytic or unclassifiable appearance, respectively. The TdT assay may be helpful to identify such cells of unknown origin and in addition may provide the means of discrimination between such cases and ALL patients who mostly show high TdT activities. Another result of our studies was the finding of moderate TdT activity of 1.2 U/mg with cells from the pleural effusion of a patient with Hodgkin's disease. Cells from malignant effusions from a patient with melanoma and a patient with teratoid carcinoma showed no TdT activity. Cells form the peripheral blood and from the bone marrow of a patient with blast crisis of CML showed TdT activity of 1.52 and 2.72 U/mg, respectively. Two other patients with blast crisis were negative. Not TdT activity was found in leukemic plasma cells. Our results show that lyophilized cells can be used for determinations of TdT activity. This greatly facilitates multi-parameter studies including cytological, cell surface marker and biochemical analyses.
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PMID:Terminal deoxynucleotidyl transferase (TdT) and membrane receptors in human leukemia and lymphoma -- first experience with lyophilized cells. 694 60

Marrow culture studies revealed a spectrum of qualitative and quantitative defects in granulocyte-macrophage progenitors (GM-CFC) of patients with chronic myeloid leukemia in chronic phase and blastic crisis. Parallel culture studies and terminal transferase determinations revealed that a significant proportion of patients in blastic crisis possess two coexisting acute phase clones, one lymphoblastic and one myeloblastic. Measurement of response to and production of T cell growth factor showed that the leukemic blast cells from patients with TdT-positive blastic crisis produced the factor, but did not exhibit a proliferative response to exogenous factor. This phenotype was identical to that observed in TdT-positive acute lymphoblastic leukemia. Additional regulatory defects were identified in CML, since leukemic GM-CFC proliferation was resistant to inhibition by concentrations of prostaglandin E, which are markedly inhibitory for normal GM-CFC. The self-renewal or recloning capacity of GM-CFC was also identified as a unique feature of some patients with CML. The addition of retinoic acid to primary cultures of leukemic GM-CFC completely abolished this recloning capacity.
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PMID:Phenotypic evaluation of chronic myeloid leukemia. 694 81

The importance of determination of the activity of TdT is discussed in the light of a case of chronic myeloid leukaemia in a patient aged 55 years in whom after 4 years from the onset of the disease blastic crisis developed. High TdT activity was correlated with other features of blastic crisis of lymphoid character and with good response to vincristine and prednisone. This enzyme which is a valuable marker of lymphoblasts can predict also blastic crisis and give cues as to proper treatment.
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PMID:[Terminal DNA nucleotidyltransferase in blastic crisis in myelocytic leukemia]. 694 63

A Ph1 chromosome positive chronic myeloid leukemia patient whose chronic phase lasted 7.5 years experienced a blastic transformation originating in the spleen. The spleen was infiltrated with undifferentiated blast cells that on cytogenetic analysis had a hyperdiploid karyotype and were Ph1 chromosome positive. The blast cells were negative for PAS, peroxidase. Sudan black and esterase stains. They were non-T, non-B with TdT activity. Remission was achieved in response to prednisone, vincristine, and adriamycin. Ph1 positive cells were present with cells responding to PHA stimulation throughout the course of the disease. A Giemsa-11 staining procedure male possible the ascertainment of a No. 9 translocation chromosome in blastic crisis cells that had also been present in Ph1 chromosome positive cells early in the disease. The presence of this translocation initially in myeloid cells and subsequently in apparent lymphoid cell types suggests the origin of this patient's leukemia as a pluripotential stem cell.
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PMID:9;22;15 complex translocation in Ph1 chromosome positive CML revealed by Giemsa-11 procedure in apparent lymphoid cells of blastic crisis. 694 32

The level of sialyltransferase activity in leukaemic blasts from acute lymphoblastic leukaemia (ALL) cases was significantly lower (3.29 +/- 2.09 pmoles/5 X 10(7) cells or 1.77 +/- 1.16 pmoles/mg protein) than those (18.80 +/- 4.91 pmoles/5 X 10(7) cells or 7.72 +/- 1.75 pmoles/mg protein) of mature lymphocytes from normal volunteers (T less than 0.001). An inverse relationship between the level of sialyltransferase activity and the level of terminal transferase (TdT)activity was seen in blasts from eight TdT-positive ALL cases. No significant difference was observed in the level of sialyltransferase activity between ALL and cells of chronic myelogenous leukemia (CML) in blast crisis. Short Term culture of ALL blast cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) at the concentration of 10-(6)M to 10-(9)M caused a marked increase in sialyltransferase activity. In one of these three ALL cases the population of TdT-positive cells and the TdT activity of the blasts decreased significantly after culture with TPA. These results suggest that biochemical differentiation of leukaemic lymphoblasts has been induced by the addition of TPA, although morphological changes were not observed. Sialyltransferase activity may be a useful indicator for the analysis of differentiation of lymphocytes.
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PMID:Sialyltransferase activity as a marker for the differentiation of lymphocytes. Increase in sialyltransferase activity of blasts from acute lymphoblastic leukaemia cases by 12-o-tetradecanoylphorbol-13-acetate (TPA). 695 64

Phenotypic changes in blast crisis of a case of Philadelphia chromosome (Ph1)-positive chronic myelogenous leukaemia were characterized by serial terminal transferase (TdT) determinations simultaneously related to cytochemical and cytogenetic data. At the onset of the blast crisis, 90% of the blast cells were acid phosphatase-positive (focal pattern), Ph1-positive, lymphoid cells. The TdT activity amounted to 29 units/10(8) mononuclear cells in the peripheral blood and to 57 units/10(8) mononuclear cells in the bone marrow. Therapy with vincristine and prednisone caused the elimination of the TdT-positive cell population. 4 months later, there was an increase in TdT-negative, myeloid blasts which was brought under control with busulfan. Cytogenetic analysis of the myeloid blasts still revealed Ph1 positivity in 100% of the metaphases examined and the lack of additional chromosomal abnormalities. A second relapse was again dominated by TdT-containing cells with the 46,XX,Ph1 karyotype. This time, the patient failed to achieve remission with vincristine and prednisone. Even though the TdT activity was markedly decreased, the lymphoid blast count remained elevated and the cells showed resistance to further therapy. This failure of morphology, cytochemistry as well as cytogenetics to distinguish between the individual phenotypes emerging during the course of blast crisis of CML characterized the TdT as a cell marker of important diagnostic and therapeutically prognostic value.
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PMID:Phenotypic changes in a case of blast crisis of CML: characterization by TdT, cytochemistry, and cytogenetics. 695 37

Peripheral blood cells from 9 E- and 6 D+ SIg- ALL patients and from 11 CML patients in TdT+ blastic crisis were subjected to discontinuous albumin gradient separation according to Dicke's method, and TdT assayed in the six fractions recovered therefrom. The major results were: (i) in E- ALL and in CML-BC, TdT+ cells could be recovered either within a narrow range of specific densities or were spread over most of the gradient, which might suggest differences in cell maturation among the patients; (ii) in some instances, most leukemic blasts were found in TdT-negative or faintly positive fractions; (iii) in most, but not all, E- All and BC, the majority of TdT+ cells was found in low density fractions; (iv) all E+ ALL had high density TdT+ cells. Cell Fractions of most patients were also examined at the electron microscope, and correlations between morphology and marker characterization were tentatively drawn.
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PMID:TdT-positive and TdT-negative human leukemic cells: specific density and morphology. 695 9


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