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

The carbohydrate antigen 3-fucosyl-N-acetyl-lactosamine (FAL) is expressed on human granulocytes and is detected by a monoclonal antibody B4.3. After neuraminidase treatment, this structure can also be detected on monocytes and on the cells of nearly all acute myeloid leukemia patients (38/39). It is then also present on the cells of a number of CALLA-positive lymphatic leukemias (8/18), but not on T-ALL and B-ALL cells. On cells of patients with AUL, the antigen is then detected in many TdT+ cases, but not in TdT- cases.
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PMID:Detection of the granulocyte-specific antigen 3-fucosyl-N-acetyl-lactosamine on leukemic cells after neuraminidase treatment. 619 17

A murine hybridoma-derived monoclonal antibody, PM-81, was obtained from a fusion of cells of the NS-1 myeloma cell line with cells from a mouse immunized with the HL-60 promyelocytic leukemia cell line. This cytotoxic IgM monoclonal antibody was specific for myeloid cells. Employing indirect immunofluorescence and flow cytometry, we determined that this antibody reacts strongly with normal human granulocytes, eosinophils, and monocytes but not lymphocytes (including phytohemagglutinin-activated lymphocytes), null cells, red blood cells, or platelets. Moreover, the PM-81 antibody reacts with leukemia cells from 19 of 22 patients with acute myelocytic leukemia of all FAB subclasses, three of three patients with common acute lymphocytic leukemia, four of four patients with chronic myelocytic leukemia (CML) in myeloid blast crisis (terminal transferase (TdT)-negative) but did not react with cells from two patients with CML in lymphoid blast crisis (TdT-positive) or five patients with chronic lymphocytic leukemia. The myeloid cell lines HL-60, K562, KG-1, and U937 were all reactive with PM-81. The lymphoid lines CCRF-CEM and Daudi did not express PM-81 but HSB-2 was positive. The PM-81 antigen was absent on myeloid and erythroid progenitor cells as determined by their insusceptibility to complement-dependent lysis. In addition, only PM-81-unreactive cells were capable of colony formation. Furthermore, the PM-81 antibody does not appear to induce modulation of the antigen to which it binds. Thus, this monoclonal antibody appears to fulfill several criteria for clinical utility in the diagnosis and treatment of both acute myelocytic and acute lymphocytic leukemia.
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PMID:A unique antigen expressed on myeloid cells and acute leukemia blast cells defined by a monoclonal antibody. 657 89

The authors have determined TdT levels in a case of Ph1-positive AML. Peripheral blood cells and bone marrow cells taken during the various phases of the disease were examined. Liquor cells were analyzed when symptomatic central nervous system involvement occurred. High TdT levels were found in all of the phases of the disease including the liquor. TdT eluted at various isoelectric points indicating a shifting of the activity to greater molarity during progress of the disease. Two different forms of TdT were present in the liquor. The authors speculate about the existence of a relation between TdT levels and Ph1-positive leukemia. They point out the importance of TdT levels as functional criterion of remission in acute leukemia. Finally, the existence of different forms of TdT could be the expression of a clonal selection caused by therapy or of a spontaneous clonal competition.
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PMID:Ph1-positive acute myelocytic leukemia with high TdT levels. 657 48

The clinical, hematologic, and cytogenetic features of ACML in children appear to be identical to Ph1-positive CML seen in adults. From our review of the literature, one could anticipate that a child with this condition would have a response to therapy and an anticipated survival similar to that seen in adults. This situation is quite different when one compares adults with ALL to children with the same disease. It has been suggested that Ph1-positive CML is an acquired, postzygotic abnormality induced by environmental agents. It is difficult to reconcile this hypothesis with the fact that this condition can be seen in infants as young as 5 months of age and the general belief that environmental carcinogens take many years to produce malignant changes in cells. Ph1-positive CML has been associated with atomic bomb exposure and it is of interest to note that two patients in the present series had received radiation. For both children and adults, bone marrow transplantation during the chronic phase is the most successful therapy if a suitable donor is available. Recently, successful marrow transplantation during the accelerated phase has also been reported. For patients without a suitable donor, control of the disease with either busulfan or hydroxyurea and attempts to induce a remission with chemotherapy during the accelerated or blast phase is the best current alternative. For patients whose blasts have lymphoid characteristics such as TdT activity, vincristine and prednisone may be successful. For those patients with a myeloid or mixed lymphoid-myeloid transformation, no chemotherapy regimen has been successful. An aggressive approach such as that described by Weinstein et al. for the treatment of acute nonlymphocytic leukemia might prove beneficial.
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PMID:Adult-type CML in childhood: case report and review. 658 71

A retrospective study was undertaken to evaluate terminal transferase activity and glucocorticoid receptor content as predictors of prognosis in 52 adult patients with acute myeloid leukemia (AML). Eighteen patients who had detectable levels of TdT in their leukaemic cells (greater than or equal to 0.1 unit microgram-1 DNA), had a higher complete remission rate than patients with low TdT activity. Patients below 60 years with increased TdT activity also had longer survival as compared to those with low TdT levels. By combining cytochemical analysis of peroxidase and immunocytochemical staining for TdT it was possible to show that the enzyme was located in leukaemic cells of myeloid origin. Leukemias of monocytic origin had no detectable TdT activity in 10/11 cases. The cellular content of the cytoplasmic glucocorticoid receptor varied from 0 to 2.8 fmol micrograms-1 DNA. There was no difference in receptor content between the different FAB subgroups. High levels of the receptor (greater than or equal to 0.22 fmol microgram-1 DNA) were positively correlated with the remission rate. Patients with TdT levels of greater than or equal to 0.1 unit microgram-1 DNA and a glucocorticoid receptor concentration of greater than or equal to 0.22 fmol microgram-1 DNA had significantly higher remission (P = 0.001) and survival rates (P = 0.007) compared with those with undectectable levels of both TdT and low receptor content. It is thus concluded that combined measurements of TdT and the glucocorticoid receptor are useful predictors of prognosis in AML.
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PMID:Prognostic significance of terminal transferase activity and glucocorticoid receptor levels in acute myeloid leukemia. 659 93

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

Increased TdT activity was demonstrated in 2 cases of AML. One of them had Ph1 positive chromosome due to a standard translocation of t(9:22). Treatment with cytosine arabinoside, daunorubicin, 6-mercaptopurine and prednisolone was ineffective or only partially effective. Switching to the vincristine and prednisolone therapy resulted in a complete remission in both cases.
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PMID:Two cases of acute myelogenous leukemia with high terminal deoxynucleotidyl transferase activity responding to vincristine-prednisolone treatment with complete remission. 695 Oct 69

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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