Enzymic characterizations of leukocytes in acute lymphocytic leukemia.
Item
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Title
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Enzymic characterizations of leukocytes in acute lymphocytic leukemia.
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Identifier
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AAI8820898
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identifier
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8820898
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Creator
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Russo, Sandra Ann.
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Contributor
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Adviser: Olga Greengard
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Date
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1988
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Biochemistry
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Abstract
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Thymidine kinase (TK), the proportion of its isozymes (TK1, TK2), and {dollar}\gamma{dollar}-glutamyltranspeptidase (GGT) were studied in peripheral white blood cells and bone marrow from children with acute lymphocytic leukemia (ALL). Of the 47 cases, 43 were classified as early pre-B cell ALL. The blood lymphoid fraction of ALL (as compared to normal) subjects showed significant elevations in the activity of TK, and in the ratio of its isozymes 1 and 2. The GGT activity of the same homogenates was significantly below normal, and this was also revealed in whole cells assayed with a fluorimetric method we adapted for use in flow cytometric analysis and sorting of leukocytes on the basis of GGT content.;During chemotherapy induced remission, the enzyme concentrations in ALL blood lymphocytes (as well as bone marrow) became normalized, and changed again toward the untreated values during relapse. The proportion of TK isozymes followed a similar pattern, but TK (and GGT) activities were more sensitive indicators of disease state. Over the untreated and relapsed population, the number of lymphocytes as well as of blasts per ml blood correlated significantly with the lymphocyte fraction's TK and (in the opposite sense) GGT activity per mg protein. Elevated TK and subnormal GGT was also exhibited, however, by the blast free preparation from several relapsed or untreated patients, indicated the presence (to varying extents) of a subpopulation of maldifferentiated or functional defective (but morphologically normal) lymphocytes. Incubations of ALL lymphocytes with mitogens resulted in blast formation, and in variable (often striking) increases of TK as well as thymidine incorporation, but (unlike in lymphocytes from normal subjects) PWM failed to stimulate GGT activity. This enzyme was also diminished in the granulocytes (and bone marrow) of ALL subjects; in one third of the cases it was 10-20% of normal.;The results of this investigation indicate that quantification of GGT and TK in blood leukocytes (1) detects functional abnormalities in lymphocytes that are not evident by microscopic examination, (2) reveals disease heterogeneity in subjects with the same ALL (as judged by antigen typing) and similar hematological characteristics, and (3) contributes objective criteria to monitoring the treatment efficacy and predicting relapse.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
