LIGATION OF CELL-SURFACE CD38 PROTEIN WITH AGONISTIC MONOCLONAL-ANTIBODY INDUCES A CELL-GROWTH SIGNAL IN MYELOID-LEUKEMIA CELLS

CD38 is expressed during early stages of differentiation in normal and leukemic myeloid cells. Recently, CD38 has been shown to participate in intracellular signal transduction pathways following its ligation w ith CD38-specific mAbs, In this study me report that ligation of CD38 by one such agonistic mAb (IB4) induced proliferation of cultured leuk emic cells in vitro, In HL-60, KG-IA, NB4, and OCI-AML-3 myeloid leuke mia cell lines, IB4 mAb induced an increase in the proliferating cell fraction as determined by cell number, clonogenic assay, and Bow cytom etric analysis, The presence of Ab caused a dose-dependent increase in the number of CFU and an increase in cell divisions, HL-60-Dox cells (a HL-60-doxorubicin-resistant cell line), which have no detectable CD 38 expression, failed to respond to IB4 mAb, The effect of CD38 ligati on on cell growth was also evaluated in freshly isolated leukemic cell s front patients with acute myelogenous leukemia (AML), A significant increase in the proliferating cell fraction (S+G(2)M) was observed in 50% of the patients incubated with IB4 mAb, In five of the six AMI; pa tients, anti-CD38 mAb stimulated the proliferation of AML colony-formi ng cells. These results suggest that ligation of CD38 can induce the p roliferation of leukemic cells and may play a role in the propagation of leukemic cell clones in certain cohorts of AML patients.