CD38 EXPRESSION DISTINGUISHES 2 GROUPS OF B-CELL CHRONIC LYMPHOCYTIC LEUKEMIAS WITH DIFFERENT RESPONSES TO ANTI-IGM ANTIBODIES AND PROPENSITY TO APOPTOSIS

The expression of CD38 by B cells of chronic lymphocytic leukemia (B-C LL) was studied in 20 untreated patients. The cells expressed abundant CD38 (relative fluorescence intensity range, 6 to 15) in 6 cases (gro up I patients), whereas CD38 expression was low to absent (relative fl uorescence intensity range, 0 to 3) in the remaining cases (group II p atients). Exposure of the cells from group I patients to goat antihuma n mu chain antibodies (Ga mu-ab) resulted in the elevation of intracel lular free Ca2+ concentration ([Ca2+](i)) followed by apoptosis. In co ntrast, exposure of group II cells to Ga mu-ab was not followed by inc reased levels of [Ca2+](i), programmed cell death or cell proliferatio n. No differences in the expression of surface IgM were noted in the t wo groups of B-CLL cells. Normal peripheral blood B cells, which expre ssed low to absent CD38, were capable of mobilizing [Ca2+](i) and of p roliferating after exposure to Ga mu-ab. The collected data suggest th at, although group I B-CLL cells were able to transduce the signals de livered by IgM crosslinking, this pathway was severely impaired in gro up II B-CLL cells. However, unlike that observed in normal circulating B cells, stimulation of group I cells with Ga mu-ab resulted in apopt osis rather than proliferation, CD38 did not appear to be directly inv olved in [Ca2+](i) mobilization induced by Ga mu-ab in group I B-CLL c ells because their exposure to anti-CD38 monoclonal antibodies failed to cause [Ca2+](i) mobilization or to block the [Ca2+](i) response ind uced by Ga mu-ab. These data indicate that CD38 expression identifies a particular subset of B-CLL cells with defined functional properties, including the propensity to undergo apoptosis. (C) 1996 by The Americ an Society of Hematology.