Regulation of CD38 in proliferating chronic lymphocytic leukaemia cells stimulated with CD154 and IL-4

Background and Objectives Chronic lymphocytic leukemia (CLL) cells, like normal B-cells, exist in two populations in vivo : quiescent cells in the peripheral circulation and proliferating cells in lymph nodes. The surface marker CD38 has roles in cell adhesion and signaling. Its expres- sion correlates with poor clinical outcome and is associated with expression of the signaling intermediate ZAP-70, which is also a marker of poor prognosis. We investi- gated the regulation of CD38 and ZAP-70 in proliferating CLL cells. Design and Methods W e cultured CLL cells on a stromal cell la yer that maintains viability and also with some stromal cells expressing CD40 ligand (CD154) in order to measure changes in expression of CD38 and ZAP-70. Results W e demonstrated up-regulation of CD38 expression b y CD154. The degree of up-reg - ulation did not cor relate with clinical stage or mutational status. In addition in the majority of cases tested ZAP-70 expression increased in parallel with up-regulation of CD38 although discordant cases were also observed. Interpretation and Conclusions Overall w e demonstrated that regulation of CD38 in CLL is dynamic and dependent on signals from CD154 and a stromal cell la yer . W e speculate that CD38 and ZAP-70 are expressed in lymph node leukemic cells in both good and poor prognosis patients, but, in cases with good clinical outcome, these molecules are down-regulat- ed in the peripheral blood whereas in cases with poor prognosis their expression is maintained