CYTOLYTIC ACTIVITY OF PERIPHERAL-BLOOD BLAST CELLS FROM PATIENTS WITHACUTE MYELOID-LEUKEMIA

The results of the present study demonstrate that cells with the morph ologic and phenotypic characteristics of blast cells that are obtained from the peripheral blood of patients with newly-diagnosed or recurre nt acute myeloid leukemia (AML) can be stimulated by gamma interferon + lipopolysaccharide (IFN/LPS) to mediate in vitro cytolysis of an NK- insensitive hepatoma cell line, The conditions of IFN/LPS induction an d subsequent assessment of cytotoxicity that were employed were identi cal to those used conventionally to test macrophage-mediated tumor cel l cytotoxicity, What was totally unexpected was that these same blast cells, in the absence of stimulation with IFN/LPS, were also found to mediate high levels of spontaneous cytotoxicity against autologous bon e marrow cells and against the U937 human promonocytic leukemia cell l ine in vitro, This high level of spontaneous cytotoxicity against auto logous bone marrow or U937 promonocytic leukemia cells was not enhance d by IFN/LPS or MCSF under conditions that stimulated cytotoxic functi on in normal blood monocytes and was markedly reduced by pretreatment of the blast cells with IL2 under conditions that induced potent NK/LA K-mediated cytotoxicity. Neutralizing antibodies against TNF alpha and /or IL1 alpha/beta eliminated the cytolytic function of blast cells ag ainst autologous bone marrow or U937 promoncytic leukemia targets. The se findings demonstrate the existence of a population of cells with th e morphologic characteristics of blast cells in the peripheral blood o f AML patients which has the capacity to mediate spontaneous cytolysis of autologous bone marrow cells or a promonocytic leukemia cell line. These cells may be an immature variant of normal precursors produced as a consequence of the disordered hematopoietic environment in the ma rrow of AML patients. Alternatively, this function may be mediated by a subset of the leukemic blasts themselves.