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 ψgt;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. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

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. © 1987 S. Karger AG, Basel