Maturation and apoptosis of primary human acute myeloblastic leukemia cells are determined by TNF-alpha exclusively through CD120A stimulation

Background and Objective. Tumor necrosis factor-ct plays an important role in hematopoiesis. Its effects are mediated through two membrane-bound recep tors: TNF-R I (p55; CD 120a) and TNF-R II (p75; CD 120b). The aim of our st udy was to investigate the relative roles of these receptors. Design and Methods. We analyzed in 16 acute myeloid leukemia cases whether TNF-alpha could induce in vitro maturation and apoptosis. We then investiga ted which of the two receptors was provoking monocytic maturation and which was responsible for apoptosis by using the agonistic MoAb HTR-9, directed at CD120a, and the CD120b antagonistic MoAb UTR-1. Results. Monocytic maturation (morphologic and immunologic) was induced in all cases studied, although to different rates, by TNF-alpha and by HTR-9 i ncubation. The addition of UTR-1 to TNF-alpha did not abolish maturation, n or did it affect apoptosis, which was present in primary AML cultures after 4 and 10 days. Interpretation and Conclusions. We present here evidence that the sole stim ulation of CD 120a, but not of CD120b, by TNF-alpha is responsible for both monocytic maturation and apoptosis of primary AML blasts. (C) 1999, Ferrat a Storti Foundation.