A Marked Decrease of Endogenous and Activated Natural Killer Cell Activities in Childhood Acute Lymphoblastic Leukemia

Natural killer cell activity was studied in 40 children with acute lymphoblastic leukemia by ⁵¹ Cr-release assay using K562 target cells. NK cell activity of ALL at the time of onset or relapse was 9.0 ±4.9% specific lysis (n = 20), being depressed as compared with the normal value of 47.2 ± 5.7% (p < 0.01). The decrease of NK cell activity was also present in the remission phase: % specific lysis was 23.5 ± 9.2% (n = 25). The decrease was still recognized among most of the off-therapy patients. In vitro studies demonstrated that, among the conventional anti-leukemic agents, prednisolone, arabinosylcytosine and daunorubicin depressed NK cell activity. The anti-leukemic agents appear to contribute at least in part to the impaired NK cell activity in ALL. The continuous decrease of NK cell activity even after the cessation of antileukemic therapy, however, cannot be explained by their effects alone, suggesting that the NK cell impairment is one of the characteristic features of ALL. NK cells responded to interferon (IFN) but their activated activity was still below the normal endogenous activity, and they did not respond to an IFN inducer of poly I:C at the time of onset or relapse. In remission phase, NK cells responded to both IFN and poly I:C and their activated activity reached the normal endogenous level. These results certainly demonstrated a marked decrease of NK cell activity in ALL.