Cytotoxicity of purified leu 19+ cells from the peripheral blood of children with acute lymphocytic leukemia

Abstract

Several investigators have reported decreased natural killer cell activity of the peripheral blood from children with acute leukemia both at diagnosis and in relapse. This study was to determine whether this decreased natural killer activity is the result of a diminished number or defective function of natural killer cells or both. The percentage of Leu 19+ (NKH-1, CD56) and the lytic activity of a purified Leu 19+ population from the peripheral blood of children with acute lymphocytic leukemia as well as from healthy children were determined. This cell population mediates most natural killer and natural killer-like activity in the peripheral blood. Twenty-three children with acute lymphocytic leukemia (16 at diagnosis, seven in relapse) as well as six control children were studied. The percentage of Leu 19+ cells was significantly lower in the blood of children either at initial diagnosis (median, 3%; P less than 0.005) or in relapse (median, 1%; P less than 0.01) than that for the control children (median, 12.5%). The cytotoxicity of peripheral blood mononuclear cells (PBMC) against K562 in 3-hour 51Cr release assay was significantly lower for patients either at diagnosis (median, 8.5 lytic units[LU]/10(7) cells; P less than 0.005) or in relapse (median, 3 LU/10(7) cells; P less than 0.005) than that for normal controls (median, 97 LU/10(7) cells). The lytic activity of a fluorescent activated cell sorter (FACS) purified Leu 19+ population was evaluated. The Leu 19+ cells were sorted from PBMC of 11 children with acute lymphocytic leukemia who had more than 2% Leu 19+ cells in their PBMC (nine at diagnosis and two in relapse). The lytic activity of sorted Leu 19+ cells was significantly (P less than 0.04) lower for patients at initial diagnosis (median, 45 LU/10(7) cells) than that for normal control children (median, 317 LU/10(7) cells). One of the two children studied at relapse had low Leu 19+ lytic activity. The authors concluded that (1) The percentage of Leu 19+ cells in the peripheral blood of the majority of children with acute lymphocytic leukemia either at diagnosis or in relapse is below normal; (2) The lytic activity of PBMC from the majority of children with acute lymphocytic leukemia is reduced both at diagnosis and in relapse; and (3) The lytic activity of Leu 19+ purified PBMC is reduced in the majority of children with acute lymphocytic leukemia. These findings confirm the defective natural killer cell profile in children with acute lymphocytic leukemia both at the time of diagnosis and in relapse.