RNase H of human leukemic cells: a new biological parameter in the study of human leukemias (review).

This article reviews the authors' investigation of the enzyme RNase H (EC 3.1.4.34.) in human leukemic cells and presents the accumulated available data, based on which this enzyme is proposed to serve as a new biological parameter in the study of progression of human leukemias. The introduction gives a brief account of the occurrence, characterization and possible biological role of RNase H in cells and in retroviruses. The results reviewed briefly concern: (1) the development of a new convenient, economic and reliable assay for normal and leukemic blood mononuclear cell RNase H, which is capable of resolving subtle activity differences between samples; (2) the differentiation of RNase H levels between normal and leukemic cells; (3) the correlation of RNase H levels from different leukemia types with the severity of the disease; (4) the correlation of RNase H levels in leukemic cells with clonogenic stages in the clonal differentiation pathway; (5) the predictive potential of a RNase H activity-based parameter (phi) in assessing progression in acute myelocytic leukemia and (6) the possibility of differentiation of the RNase H levels between normal and leukemic cells via regulation of the enzyme activity at the level of antagonistic phosphorylations mediated by cAMP and calmodulin.

A New Mononuclear Cell (MNC) RNase H Activity-Based Parameter (ψ) With Possible Prognostic Value in Assessing Progression in Acute Myeloid Leukaemia.

A new biological parameter (ψ) has been obtained and proposed here to serve in the assessment of acute myeloid leukemia (AML) progression. It is a function of the activity of RNase H (EC 3.1.4.34), the latter determined in mononuclear cells from the peripheral blood of AML patients. Using a series of patients at the time of diagnosis and after 1-2 cycles of chemotherapy, the enzyme was assayed before the several times during chemotherapy. The derivation of 4 was based on evidence suggesting that the enzyme level correlates with the proliferating leukaemic blasts and their progenitors. Values ψ>1 signify the presence of clonogenic leukaemic progenitor cells in the peripheral circulation. When these high (> 1) ψ values were found during chemotherapy, in these cases it was possible to predict an increase of the peripheral blast pool, with 82% success, occurring 5-35 days before cytologic relapse. In the patients in whom at some stage during treatment, ψ acquired values above unity or in whom ψ increased progressively, survival time was in linear correlation with the time period from the initiation of treatment to the documentation of this high ψ estimate. These results suggest that a patient's relapse risk can be defined by ψ with some degree of precision.

Activity and function of hybrid ribonuclease in cells of acute and chronic myelogenous leukemia.

The activity of hybrid ribonuclease (ribonuclease H) has been determined in mononuclear blood cells (lymphocytes plus monocytes) from 23 normal individuals and cells (pool of immature granulocytes, metamyelocytes and lymphocytes) from 35 untreated acute and chronic myelogenous leukemia cases. It was found that in 86% of the leukemic samples the activity of ribonuclease H was above two standard deviations from the mean activity level drawn for the group of normal samples along the 0-100% substrate hydrolysis scale. The activity of the enzyme in leukemic cells correlated linearly with the DNA-synthesizing activity of the cells in vitro and in the examined CML cases it paralleled the inverse relationship of the incorporation of tritiated thymidine into DNA to the size of the pool of immature granulocytes. In one CML patient who received chemotherapy with Myleran, the activity of ribonuclease H, high at the initiation of drug therapy, was reduced to a normal level at remission, but increased again at the stage of subsequent relapse. These findings indicate that the levels of ribonuclease H in leukemic cells reflect the proliferative activity of the population in the cases of untreated myelogenous leukemias.

Study of the activity of lymphocyte adenosine deaminase in chronic renal failure.

The activity of lymphocyte adenosine deaminase was studied in 28 undialysed uremic patients, 19 patients on maintenance hemodialysis and 32 normal subjects. A statistically significant decrease of the enzyme activity was found both for the undialysed and dialysed patients.